losartan-potassium and Lupus-Erythematosus--Systemic

Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease with variable clinical presentation, typically characterized by a relapsing-remitting course. SLE has a multifactorial pathogenesis including genetic, environmental, and hormonal factors that lead to loss of tolerance against self-antigens and autoantibody production. Mortality in SLE patients remains significantly higher than in the general population, in part because of the limited efficacy of available treatments and the associated toxicities. Therefore, novel targeted therapies are urgently needed to improve the outcomes of affected individuals. Erythropoietin (EPO), a kidney-produced hormone that promotes red blood cell production in response to hypoxia, has lately been shown to also possess non-erythropoietic properties, including immunomodulatory effects. In various models of autoimmune diseases, EPO limits cell apoptosis and favors cell clearance, while reducing proinflammatory cytokines and promoting the induction of regulatory T cells. Notably, EPO has been shown to reduce autoimmune response and decrease disease severity in mouse models of SLE. Herein, we review EPO's non-erythropoietic effects, with a special focus on immune modulating effects in SLE and its potential clinical utility.

Topics: Animals; Erythropoietin; Humans; Lupus Erythematosus, Systemic

Haematological abnormalities are common in systemic lupus erythematosus (SLE) and may be manifested by anaemia of different pathogenesis. The objective of this article was to describe some data concerning autoimmune haemolytic anaemia, aplastic and megaloblastic ones accompanying SLE and also to present erythropoietin (EPO) function in the above mentioned diseases. In SLE many factors are produced which disturb the organism haematological balance both on the peripheral level and in the bone marrow. It is assumed that the autoantibodies produced in SLE are the main cause of anaemia. However it should be considered that quantitative changes in the number of erythrocytes observed in this disease are also caused by chronic inflammatory condition, which as the element of autoimmune disease impairs the endocrine function of the kidneys in EPO production. It influences bone marrow, iron metabolism and then haemopoiesis. Apart from humoral factors the role of mechanisms connected with immune cellular response is also considered.

Topics: Anemia, Aplastic; Anemia, Hemolytic, Autoimmune; Anemia, Megaloblastic; Erythropoietin; Humans; Immunity, Cellular; Kidney; Lupus Erythematosus, Systemic

Patients with systemic lupus erythematosus (SLE) have relative deficiencies of the C3b/C4b receptor (CR1, CD35) on erythrocytes (E). This receptor takes part in the binding, transport and endocytosis of circulating immune complex bound complement components (ICC). Besides the autoantibodies the abnormalities in IC elimination are fundamental to the pathogenesis of SLE. During the last 15 years more than 100 patients with SLE have been treated in our Department and their data on ICC clearance by ECR1 analyzed. After plasmapheresis the ECR1 expression and also the binding sites for ICC were increased, while the level of IC and autoantibodies were reduced. Stimulating erythropoiesis in patients with anaemia and lupus nephritis caused the decreased expression and functional activity of ECR1 to be improved. In patients with SLE the level of soluble CR1 was also decreased, but a significant portion of soluble CR1 bound ICC in vivo, especially in those with severe renal lesion.

Topics: Antigen-Antibody Complex; Complement Activation; Erythrocytes; Erythropoietin; Humans; Lupus Erythematosus, Systemic; Plasmapheresis; Receptors, Complement; Recombinant Proteins

Haematological abnormalities are common in systemic lupus erythematosus. Anaemia is found in about 50% of patients, with anaemia of chronic disease being the most common form. Impaired erythropoietin response and presence of antibodies against erythropoietin may contribute to the pathogenesis of this type of anaemia. Patients with autoimmune haemolytic anaemia usually belong to a distinct category, which is associated with anticardiolipin antibodies, thrombosis, thrombocytopenia, and renal disease, often in the context of secondary antiphospholipid syndrome. Autoantibodies, T lymphocytes, and deregulation of the cytokine network can affect bone marrow erythropoiesis, leading to anaemia.

Topics: Anemia, Hemolytic, Autoimmune; Autoantibodies; Erythropoietin; Hematopoiesis; Humans; Lupus Erythematosus, Systemic; Recombinant Proteins; T-Lymphocytes

Rituximab, a monoclonal antibody directed against the CD20 molecule found on pre-B cells and mature B cells (but not on plasma cells), was introduced in the late 1990s for the treatment of non-Hodgkin's lymphoma. Recently, this antibody has been used to treat autoimmune diseases, especially those associated with a prominent humoral component and with potentially pathogenic autoantibodies. Small cohort studies have indicated that rituximab could have an important role in the management of these disorders. Rituximab has also been utilized in the transplant setting, to diminish levels of alloreactive antibodies in highly sensitized patients, to manage ABO-incompatible transplants, and to treat rejection associated with B cells and antibodies. The exact mechanism by which rituximab exerts its effects in autoimmunity and transplantation remains unclear, as specific autoantibody or alloantibody levels often seem not to diminish in parallel with clinical improvement. A role for rituximab in depleting B cells and compromising their antigen-presenting function seems likely; rituximab might also inhibit T-cell activation. A synergistic effect has been noted in vitro following administration of corticosteroids to B-cell lines, with accentuation of B-cell cytotoxicity; this observation might be relevant to certain studies, as some regimens have utilized both agents simultaneously. This article reviews the current use of rituximab in renal disease and transplantation, and includes discussion of the drug's potential role in novel therapeutic protocols.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Autoimmune Diseases; Autoimmunity; B-Lymphocytes; Erythropoietin; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Graft Rejection; Humans; Immunologic Factors; Kidney Diseases; Kidney Transplantation; Lupus Erythematosus, Systemic; Lymphoproliferative Disorders; Recombinant Proteins; Red-Cell Aplasia, Pure; Rituximab; Vasculitis

We describe a 32-year-old woman who developed severe anemia due to pure red cell aplasia in the course of systemic lupus erythematosus (SLE). After failure of therapy with high doses of glucocorticoids and immunoglobulins, and despite high levels of endogenous erythropoietin, she was treated with human recombinant erythropoietin with dramatic and sustained improvement. Based on this case and on the literature review of erythropoietin therapy in pure red cell aplasia, we suggest that erythropoietin should be used in SLE associated pure red cell aplasia before cytotoxic therapy.

Topics: Adult; Erythropoietin; Female; Humans; Lupus Erythematosus, Systemic; Recombinant Proteins; Red-Cell Aplasia, Pure

Pure red cell aplasia is a selective aplasia of the marrow erythroid cells. Unlike aplastic anemia, the marrow has a normal cellularity and the patients generally have normal leukocyte and platelet blood counts. The congenital form of the disease occurs in the firlst 1 1/2 years of life and is often responsive to corticosteroids. The acquired form may be secondary to infections, drugs, chemicals, or hemolytic anemia (aplastic crisis). In these cases it is often acute and self-limited with cessation of the infection or drug ingestion. It may also be secondary to systemic lupus erythematosus, rheumatoid arthritis, acute severe renal failure, severe nutritional deficiency, or diverse neoplasms, and may remit with treatment of the primary condition. When a thymoma is present, it should be resected since a remission is produced in 29 per cent of these patients. The remaining patients have an acquired primary form of the disease that tends to be chronic and in some cases may have an immune pathogenesis. A cytotoxic immunoglobulin inhibitor of the marrow erythroid cells or erythropoietin has been described and these patients may respond to prednisone and/or to cytotoxic immunosuppressive drugs such as cyclophosphamide and 6-mercaptopurine. Pure red cell aplasia appears to be more common than the literature has revealed and has stimulated much investigation into an immune pathogenesis for marrow failure.

Topics: Acute Kidney Injury; Anemia, Aplastic; Antilymphocyte Serum; Arthritis, Rheumatoid; Blood Cell Count; Blood Transfusion; Cyclophosphamide; Deficiency Diseases; Erythropoietin; Humans; Immune System Diseases; Infections; Lupus Erythematosus, Systemic; Mercaptopurine; Prednisone; Remission, Spontaneous; Splenectomy; Thymoma; Thymus Neoplasms

Systemic lupus erythematosus (SLE) is an autoimmune disease, which results in various organ pathologies. However, current treatment towards SLE is suboptimal. Erythropoietin (EPO) has been shown to promote SLE recovery, but clinical application can be limited by its haematopoiesis-stimulating effects. EPO-derived helix-B peptide (ARA290) is non-erythrogenic but has been reported to retain the anti-inflammatory and tissue-protective functions of EPO. Therefore, here we investigated the effects and potential mechanisms of ARA290 on SLE. The administration of ARA290 to pristane-induced SLE and MRL/lpr mice significantly suppressed the level of serum antinuclear autoantibodies (ANAs) and anti-dsDNA autoantibodies, reduced the deposition of IgG and C3, and ameliorated the nephritis symptoms. Moreover, the serum concentrations of inflammatory cytokine IL-6, MCP-1 and TNF-α in SLE mice were reduced by ARA290. Further, ARA290 decreased the number of apoptotic cells in kidney. In vitro experiment revealed that ARA290 inhibited the inflammatory activation of macrophages and promoted the phagocytotic function of macrophages to apoptotic cells. Finally, ARA290 did not induce haematopoiesis during treatment. In conclusion, ARA290 ameliorated SLE, which at least could be partly due to its anti-inflammatory and apoptotic cell clearance promoting effects, without stimulating haematopoiesis, suggesting that ARA290 could be a hopeful candidate for SLE treatment.

Topics: Animals; Cytokines; Disease Models, Animal; Erythropoietin; Female; Hematopoiesis; Inflammation; Kidney; Lupus Erythematosus, Systemic; Macrophage Activation; Mice; Mice, Inbred C57BL; Mice, Inbred MRL lpr; Oligopeptides; Phagocytosis; RAW 264.7 Cells; Terpenes

The failure of apoptotic cell clearance is linked to autoimmune diseases, nonresolving inflammation, and developmental abnormalities; however, pathways that regulate phagocytes for efficient apoptotic cell clearance remain poorly known. Apoptotic cells release find-me signals to recruit phagocytes to initiate their clearance. Here we found that find-me signal sphingosine 1-phosphate (S1P) activated macrophage erythropoietin (EPO) signaling promoted apoptotic cell clearance and immune tolerance. Dying cell-released S1P activated macrophage EPO signaling. Erythropoietin receptor (EPOR)-deficient macrophages exhibited impaired apoptotic cell phagocytosis. EPO enhanced apoptotic cell clearance through peroxisome proliferator activated receptor-γ (PPARγ). Moreover, macrophage-specific Epor(-/-) mice developed lupus-like symptoms, and interference in EPO signaling ameliorated the disease progression in lupus-like mice. Thus, we have identified a pathway that regulates macrophages to clear dying cells, uncovered the priming function of find-me signal S1P, and found a role of the erythropoiesis regulator EPO in apoptotic cell disposal, with implications for harnessing dying cell clearance.

Topics: Animals; Apoptosis; Cell Line; Erythropoietin; Female; Immune Tolerance; Lupus Erythematosus, Systemic; Lysophospholipids; Macrophage Activation; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Paracrine Communication; Phagocytosis; PPAR gamma; Receptors, Erythropoietin; Signal Transduction; Sphingosine

Phagocytes clear dying cells within an organism to prevent damaging inflammation and autoimmunity. In this issue of Immunity, Luo et al. (2016) describe how "find-me" signals from apoptotic cells induce erythropoietin signaling within macrophages to prime them for efferocytosis.

Topics: Animals; Erythropoietin; Female; Lupus Erythematosus, Systemic; Lysophospholipids; Macrophages; Receptors, Erythropoietin; Sphingosine

Erythropoiesis-stimulating agents (ESAs) play an important role in the management of anemia in patients with chronic kidney disease, but the goals cannot be reached in 5% to 10% of the patients despite high-dose ESA treatment. In case of ESA resistance, all causes of anemia encountered in the general population should be carefully reviewed. We present a patient examined for ESA resistance that was diagnosed with systemic lupus erythematosus and subsequently showed improvement of anemia with systemic corticosteroids.

Topics: Adult; Anemia; Erythropoietin; Female; Hematinics; Humans; Lupus Erythematosus, Systemic; Renal Dialysis; Renal Insufficiency, Chronic; Young Adult

Topics: Animals; Erythropoietin; Female; Lupus Erythematosus, Systemic; Lysophospholipids; Macrophages; Receptors, Erythropoietin; Sphingosine

Topics: Acute Kidney Injury; Adult; Blood Component Transfusion; Bone Marrow; Cell Lineage; Combined Modality Therapy; Darbepoetin alfa; Erythropoietin; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematuria; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Lymphohistiocytosis, Hemophagocytic; Male; Mycophenolic Acid; Myelodysplastic Syndromes; Pancytopenia; Pericarditis; Prednisone; Proteinuria; Recombinant Proteins

To analyze the frequency and causes of anaemia in systemic lupus erythematosus (SLE) patients attending in department of medicine at tertiary care hospitals.. This retrospective, descriptive and analytical study was planned to analyze the frequency and causes of anaemia in SLE patients attending the department of medicine at (MMC) and (LUMHS) hospitals during the period of Jan 2006 to Nov 2008. The criteria used in this study were from the American College of Rheumatology. Investigations recorded were blood complete picture, absolute values, peripheral smear, and reticulocyte count in all patients of anaemia. These investigations were necessary to analyse the cases of anaemia in SLE. All investigations were not done in all cases. Patients with hypochromic microcytic anaemia were advised to have serum iron and ferritin levels, seven patients with macrocytic anaemia were advised to have direct and indirect coomb's test, LFTs, serum LDH, serum B12 and folate levels. Patients with normochromic and normocytic anaemia were considered to have anaemia of chronic disease. Bone marrow aspiration and Hb electrophoresis were done in two patients with anaemia of chronic disease. Thirty adult patients were included in this study. Special proforma were prepared to record the information from case sheets of patients including basic information, symptomatology and laboratory investigations. Severity and various types of anaemias were recorded. Anaemia was graded according to severity, as mild (Hb 10-12 G/dl), Moderate (Hb 8-10 G/dl) and severe (Hb < 8 G/dl). Haemoglobinopathies and other types of anaemias were excluded from study.. Thirty adult diagnosed patients of SLE, were included. Their ages ranged from twenty years to fifty years at time of presentation. The mean age +/- SD (range) was 28 +/- 6.22 (20-50) years and median age was 31 years. Out of thirty patients, twenty seven (90%) were females and three (10%) were males. Twenty eight (93.33%) patients presented with anaemia, 14 (46.66%) patients were of mild anaemia, 8 (26.66%) patients were of moderate grade anaemia and 6 (20%) patients had severe anaemia. Iron deficiency anaemia was found in 9 (30%) patients, 12 (40%) patients had anaemia of chronic disease and 7 (23.33%) patients had haemolytic anaemia, out of theses 7 patients, 5 (16.66%) patients had Coomb's positive haemolytic anaemia. All thirty patients had ANA positive titres > 1:80; and nineteen (63.33%) patients had anti ds DNA positive, titres > 1:10.. Haematologic abnormalities are common manifestations in patients with SLE. Most patients exhibit anaemia at some point during their disease course.

Topics: Adult; Anemia; Erythropoietin; Female; Hospitals, Teaching; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Pakistan; Retrospective Studies; Severity of Illness Index; Young Adult

A 42-year-old woman with systemic lupus erythematosus was admitted to our hospital because of severe anemia. Her bone marrow was almost normocellular and erythroblasts were nearly absent. Laboratory data showed elevated levels of lactate dehydrogenase and positive findings on Coombs' tests. On the basis of these findings, her anemia was diagnosed as the overlap of pure red cell aplasia with autoimmune hemolytic anemia. Radioimmunoprecipitation assay revealed that her serum was positive for anti-erythropoietin antibodies before therapy. Furthermore, the autoantibodies inhibited proliferation of an erythropoietin-dependent cell line in a dose-dependent manner. Immunosuppressive treatment improved the anemia accompanied with disappearance of the autoantibodies.

Topics: Adult; Anemia, Hemolytic, Autoimmune; Antibody Specificity; Autoantibodies; Bone Marrow; Cell Division; Cell Line; Erythroid Precursor Cells; Erythropoietin; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Methylprednisolone; Prednisolone; Red-Cell Aplasia, Pure

Topics: Erythropoietin; Humans; Lupus Erythematosus, Systemic; Nervous System; Neuroprotective Agents

Assays for the analysis of antierythropoietin antibodies (anti-EPO Abs) currently suffer from a high degree of nonspecificity or are cumbersome and time consuming to perform. They are therefore not well suited for the analysis of large numbers of human sera samples, a task that has become increasingly important due to an increase in the number of patients developing anti-EPO Abs. The objective of this study was to develop and validate a sensitive and specific ELISA for the determination of anti-EPO Abs that would suit these purposes. In this new double antigen bridging ELISA, anti-EPO Abs bind via one site to recombinant human erythropoietin (rhEPO)-biotin immobilized to streptavidin-coated microtiter plates (MTPs) and by a second site to rhEPO labelled with digoxigenin (DIG). The amount of bound antibody is determined using an anti-DIG antibody coupled to peroxidase. A rabbit polyclonal anti-EPO Ab purified by immunoadsorption is used as reference antibody preparation. The dynamic range of this ELISA was 1-75 ng/ml per assay calibrated with the reference antibody preparation. The assay was specific for anti-EPO Abs and did not react with other immunoglobulins (Ig) present in human serum. The lower limit of detection (LLD) of the assay was 0.5 ng/ml, and the lower limit of quantitation (LLQ) was 1.0 ng/ml. Anti-EPO Abs could be detected in the sera of pure red cell aplasia (PRCA) patients. In contrast to previous reports, no anti-EPO Abs could be detected in the sera of patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS), or in the sera of dialysis patients.

Topics: Animals; Antibodies; Biotin; Digoxigenin; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Humans; Lupus Erythematosus, Systemic; Peroxidase; Rabbits; Recombinant Proteins; Red-Cell Aplasia, Pure; Reference Standards; Reference Values; Renal Dialysis; Reproducibility of Results; Sensitivity and Specificity; Sjogren's Syndrome; Streptavidin

This study was performed to assess erythropoietin levels and anti-erythropoietin antibodies in patients with systemic lupus erythematosus (SLE).. The sera of 100 patients with SLE were investigated for serum erythropoietin levels and the presence of anti-erythropoietin antibodies by ELISA. Routine laboratory parameters such as peripheral blood count, relevant parameters of blood chemistry, and immunological parameters of SLE were recorded.. Erythropoietin levels were significantly decreased in SLE patients when related to individual haemoglobin and haematocrit values (P<0.001), suggesting an inadequate erythropoietin response in SLE. Anti-erythropoietin antibodies were found in 46% of SLE patients, and erythropoietin levels (but not haemoglobin or haematocrit values) were significantly decreased in these patients compared with patients without anti-erythropoietin antibodies. Serum erythropoietin concentration as determined by ELISA was reduced in the presence of anti-erythropoietin antibodies. Furthermore, anti-erythropoietin antibodies also correlated with younger age, decreased serum levels of complement factors C3 and C4 and elevated anti-double-stranded DNA antibodies.. We conclude that the anaemia of SLE is characterized by an inadequate erythropoietin response. Anti-erythropoietin antibodies are frequently present in SLE and interfere with the measurement of serum erythropoietin level. However, these antibodies are not associated with increased severity of SLE-associated anaemia.

Topics: Adolescent; Adult; Aged; Anemia; Autoantibodies; Cross-Sectional Studies; Erythropoietin; Female; Hematocrit; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged

Topics: Acute Disease; Adult; Antibodies; Diagnosis, Differential; Erythropoietin; Female; Humans; Lupus Erythematosus, Systemic; Red-Cell Aplasia, Pure

To study the prevalence of different causes of anaemia in patients with systemic lupus erythematosus (SLE) and their associations with immunological and clinical parameters and to evaluate the contribution of erythropoietin (Epo) and anti-erythropoietin (anti-Epo) autoantibodies to the development of SLE anaemia.. 132 SLE patients with anaemia (defined as haemoglobin of 12 g/dl or less for women and 13.5 g/dl or less for men) from among a total of 345 consecutive SLE patients were prospectively enrolled into the study. Standard haematological and immunological tests were performed and serum Epo and anti-Epo antibodies were assayed.. The identified causes were anaemia of chronic disease (ACD) n=49 (37.1%), iron deficiency anaemia (IDA) n = 47 (35.6%), autoimmune haemolytic anaemia (AHA) n = 19 (14.4%) and other causes n = 17 (12.9%). There was significant heterogeneity in the severity of anaemia between the four groups (p<0.01) with AHA cases being on average more severe. The proportion of patients with anticardiolipin antibodies, low complement levels and anti-dsDNA differed significantly among the four groups; these markers were particularly common in patients with AHA, and uncommon in patients with IDA. Twenty one of 100 tested patients had anti-Epo antibodies. Such antibodies were seen practically only in patients with ACD (odds ratio 3.1, p = 0.041) and in patients with high lupus activity (ECLAM) scores (odds ratio 1.27 per point, p = 0.055). Epo response was inadequate in 42.4% and 41.2% of patients with ACD and AHA, respectively.. Anaemia in SLE usually takes the form of ACD and IDA, however autoimmune haemolysis is not uncommon. SLE patients with different causes of anaemia differ in regard to several immunological parameters. Epo response is blunted in anaemic SLE patients, particularly those with ACD and AHA.

Topics: Adult; Anemia; Anemia, Hemolytic, Autoimmune; Anemia, Iron-Deficiency; Autoantibodies; Erythropoietin; Female; Follow-Up Studies; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Prospective Studies

Neonatal lupus erythematosus (NLE) is an inflammatory syndrome in the fetus or neonate associated with the presence of anti-Ro(SSA) and anti-La(SSB) antibodies in the mother. It is characterized by a combination of dermatologic, hematologic, hepatic, and cardiac manifestations. NLE has been reported in twins; we describe neonatal lupus erythematosus occurring in triplets.

Topics: Adrenal Cortex Hormones; Antibodies; Autoantigens; DNA; Erythropoietin; Humans; Immunoglobulins, Intravenous; Infant, Newborn; Lupus Erythematosus, Systemic; Platelet Count; Platelet Transfusion; Ribonucleoproteins; RNA, Small Cytoplasmic; Skin Diseases; Triplets

In this case report we describe two patients with pure red cell aplasia (PRCA) as an initial manifestation of systemic lupus erythematosus (SLE). Antibodies to erythropoietin were determined, by an ELISA method developed in our laboratory, in frozen serum obtained from one of the patients. A high titer of antibodies to erythropoietin was detected in serum obtained before treatment with high dose intravenous immunoglobulin (IVIG). The antibody titer declined after successful treatment. This observation suggests that antibodies to erythropoietin may contribute to the pathogenesis of SLE associated PRCA.

Topics: Adult; Antibodies; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Humans; Lupus Erythematosus, Systemic; Red-Cell Aplasia, Pure

A 35 y old woman with severe and progressive systemic lupus erythematosus (SLE) received high-dose chemotherapy followed by a T cell depleted autologous stem cell transplantation. Peripheral blood stem cell were mobilised with Cyclophosphamide 4.5 g/m2 followed by Granulocyte-Colony Stimulating Factor (G-CSF). A CD34 positive selection provided a 3 log T cell depletion. High-dose immunosuppression consisted of the BEAM regimen. The purified autograft was reinfused on day 0. In the post transplant period, hemopoietic growth factors, G-CSF, Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Erythropoietin, were administered, engraftment was rapid. Both the mobilisation and the transplant procedures were easily performed and well tolerated. One year later, the patient is in clinical remission. The ANA and anti-SSA-antibodies were undetectable at 1 and 6 months after intensification, but reappeared at low levels at 9 months. Corticosteroid requirement has gradually decreased. In conclusion, we report here the favourable evolution of a patient with a severe SLE, who clinically improved with high-dose immunosuppressive therapy and autologous stem cell transplantation, and showed a 9 month serological remission.

Topics: Adult; Antigens, CD34; B-Lymphocytes; Cyclophosphamide; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mouth Mucosa; Stomatitis; T-Lymphocytes; Transplantation, Autologous; Treatment Outcome

The diagnosis and management of porphyria cutanea tarda (PCT) is complicated when it occurs in the context of renal failure, chronic hemodialysis, and anemia. We report a case of a woman who presented with painful acral blisters and hyperpigmentation. Her medical history included systemic lupus erythematosus, chronic hepatitis C infection, and renal failure necessitating chronic hemodialysis with a baseline anemia. A highly elevated serum porphyrin level led to the diagnosis of PCT. Treatment with small repeated phlebotomies and concomitant administration of erythropoietin was effective in managing her PCT.

Topics: Adult; Erythropoietin; Female; Follow-Up Studies; Hepatitis C, Chronic; Humans; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Phlebotomy; Porphyria Cutanea Tarda; Renal Dialysis; Risk Assessment

A 46-year-old man was admitted to our clinic because of acute heart failure. Six years before admission he was pointed out cardiomegary and hematuria. One year later, he was diagnosed as having jugular foramen syndrome. On admission, he had a fever and dyspnea. Pansystolic blowing murmur was audible at the apex. The chest ratio on his chest X-ray was 52.5%. An electrocardiogram showed left ventricular hypertrophy. An echocardiogram showed marked dilatation and severe dysfunction of left ventricle. Radionuclide scanning with technetium 99 m pyrophosphate identified inflammatory change in the apex. Myocardial biopsy showed fibrotic degeneration and IgG deposits in myocardium. Blood examination showed anemia, lymphopenia. positive anti-nuclear antibody (1000 times, shaggy pattern), positive anti ds-DNA antibody and hypocomplementemia. Furthermore, proteinuria was pointed out. Renal biopsy showed focal segmental glomerulonephritis with active necrotizing lesion (type III nephritis). Lupus myocarditis and nephritis was diagnosed. After prednisolone (80 mg/day) was administered. left ventricular function and hypocomplementemia improved. The ACE inhibitor was also used for proteinuria. In spite of a little amount of blood transfusion, he showed hepatic hemosiderosis. We suspect that the cause of hemosiderosis was related chronic inflammation of active lupus. It was treated with Erythropoietin.

Topics: Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Cranial Nerve Diseases; Erythropoietin; Hemosiderosis; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Middle Aged; Myocarditis; Polyneuropathies; Prednisolone; Syndrome

To investigate the existence of circulating autoantibodies to erythropoietin (EPO) in sera from patients with systemic lupus erythematosus (SLE), and to correlate their presence with anemia and clinical activity.. Ninety-two consecutive patients with SLE, 80 patients with rheumatoid arthritis, and 42 normal individuals were studied. The patients with SLE were categorized into 3 groups according to hemoglobin (Hgb) level: group A (45 patients with Hgb > 12 gm/dl), group B (26 patients with Hgb 10.1-12 gm/dl), and group C (21 patients with Hgb < or = 10 gm/dl). In all patients with SLE, the disease activity was evaluated using the European Consensus Lupus Activity Measurement scale. Antibodies to EPO were detected using an enzyme-linked immunosorbent assay and purified recombinant human EPO as antigen. The specificity of the method was evaluated with homologous and cross-reactive inhibition assays.. Antibodies to EPO were found in 15.2% of the SLE patient sera. The distribution of these antibodies among the 3 groups of SLE patients was as follows: 8.8% (4 of 45) from group A, 15.4% (4 of 26) from group B, and 28.6% (6 of 21) from group C. The prevalence of antibodies to EPO in patients with severe anemia (group C) was statistically significantly higher compared with patients without anemia (chi(2) = 4.31, P < 0.05). Patients with antibodies to EPO had higher disease activity scores (P < 0.005) and lower levels of the C4 component of complement (P < 0.05) compared with patients without antibodies to EPO.. In this study, the presence of antibodies to EPO in the sera of SLE patients is demonstrated for the first time. The presence of these antibodies is associated with severe anemia and active disease.

Topics: Adolescent; Adult; Aged; Anemia; Arthritis, Rheumatoid; Autoantibodies; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Recombinant Proteins; Sensitivity and Specificity

Topics: Adult; Anemia; Drug Resistance; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Recombinant Proteins; Renal Dialysis

Pure erythrocyte aplasia is a recognised feature of systemic lupus erythematosus (SLE); here we report two cases, one predating the onset of SLE, the other following a long period of disease quiescence. One case demonstrates the typical features of this disorder and was successfully treated with prednisolone. The second case is unusual in being resistant to immunosuppressive treatment. Bone marrow culture from the second patient revealed an inhibition of BFU-E colony formation in the presence of the patient's serum, indicating that a serum inhibitor of haemopoiesis was present. Furthermore, following T cell depletion of this patient's marrow, there was an increase in BFU-E, CFU-G and CFU-GM colony growth implicating, in addition, a possible T cell-mediated inhibition of marrow haemopoiesis. This is a novel observation and may explain the resistance shown by this patient to standard treatment.

Topics: Adult; Blood Transfusion; Bone Marrow; Cells, Cultured; Colony-Forming Units Assay; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cells; Hemoglobins; Humans; Interleukin-3; Lupus Erythematosus, Systemic; Puerperal Disorders; Red-Cell Aplasia, Pure

Previous studies of the in vitro effects of recombinant erythropoietin (rEPO) on T and B cells and studies of lymphocyte subsets in dialysis patients receiving rEPO therapy suggest that rEPO might augment immune responses. In the present study indices of autoimmunity (antinuclear antibody, anti-double-stranded DNA, and antiphospholipid antibody [immunoglobulins G and M]) were measured before, during, and after rEPO therapy in five systemic lupus erythematosus patients without renal failure (mean serum creatinine, 1.5 +/- 0.3 mg/dL). The rEPO therapy was self-administered by subcutaneous injection in doses ranging from 4,000 units once weekly to 3,000 units three times weekly for 3 to 7 months. On rEPO therapy, each patient experienced an increase in hematocrit. The mean baseline hematocrit increased from 32 +/- 2.0 to a peak of 42.2 +/- 3 (P < 0.001) at 3 to 7 months and then decreased to baseline values 1 to 2 months after rEPO was discontinued. During this time the indices of autoimmunity were not significantly changed by rEPO therapy. Systemic lupus erythematosus activity, assessed by serum C3, serum creatinine, urinalysis, and 24-hour proteinuria, also was unchanged by rEPO therapy. The rEPO therapy was generally well tolerated. However, one patient, who was also receiving replacement estrogen therapy and had high-titer antiphospholipid antibody, experienced episodes of thrombophlebitis while on rEPO therapy. In conclusion, we found no evidence that rEPO increases autoimmunity in systemic lupus erythematosus. However, we observed a temporal relationship between episodes of thrombophlebitis and rEPO therapy in a single patient with high-titer anticardiolipin antibody who was also receiving replacement estrogen therapy. These associations require further investigation.

Topics: Adult; Autoimmunity; Erythropoietin; Female; Humans; Lupus Erythematosus, Systemic; Recombinant Proteins

The expression of complement receptor Type 1 (CR1, CD35) on erythrocytes (E) is unique to humans and other primates. E-CR1, a C3b/C4b receptor that also acts as cofactor for Factor I, appears to be important in clearing C3/C4-opsonized immune complexes from the circulation, in controlling complement activation in the circulation, and in regulating antibody formation. This study was undertaken to determine whether therapy with recombinant human erythropoietin (rEPO) might increase E-CR1 expression in humans. The rationale is that young erythrocytes express more E-CR1 than old erythrocytes. Thus, conditions that stimulate erythropoiesis should increase E-CR1 expression. The hypothesis that stimulating erythropoiesis by rEPO therapy can increase E-CR1 expression was tested in six anemic chronic hemodialysis (ESRD) patients and five systemic lupus erythematosus (SLE) patients without renal failure. Before the rEPO therapy, three of the SLE patients were anemic and two were not. The ESRD patients were studied before and during 9 or 10 mo of rEPO therapy. The SLE patients were studied before, during, and after 7 mo of rEPO given by sc injection two or three times weekly. It was found that rEPO therapy was associated with a progressive increase in the average number of CR1/E in each of the ESRD patients and in the anemic SLE patients: mean baseline CR1/E was 210 +/- 50 (SE) for the ESRD patients and 125 +/- 35 for the SLE patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Anemia; Down-Regulation; Erythrocytes; Erythropoietin; Humans; Immunologic Factors; Iron; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Middle Aged; Receptors, Complement 3b; Recombinant Proteins; Transferrin

In view of the transfusional risks of viral transmission (notably HIV), autologous transfusion is increasingly used; it is often the only possible type of transfusion. A 42-year-old woman with lupus erythematosus, chronic renal failure and triple cardiac valve disease demanding surgery was admitted for multifactorial severe anaemia. Treatment with erythropoietin (8000 units/day) iron replenishment, corticosteroids and polyvalent immunoglobulins was initiated. The patient was operated upon in April 1990. A preoperative cell-saver autotransfusion was performed during surgery. The postoperative period was uneventful. Homologous transfusion was not necessary. In this case where homologous transfusion was ruled out, erythropoiesis stimulated by erythropoietin enabled autotransfusion and cardiac surgery to be performed.

Topics: Adult; Anemia; Aortic Valve Insufficiency; Blood Transfusion, Autologous; Erythropoietin; Female; Humans; Immunotherapy; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Mitral Valve Insufficiency; Tricuspid Valve Insufficiency

Topics: Anemia; Animals; Arthritis, Rheumatoid; Chronic Disease; Erythrocyte Aging; Erythropoietin; Female; Folic Acid Deficiency; Humans; Lupus Erythematosus, Systemic; Male; Recombinant Proteins; Vitamin B 12 Deficiency

A 29-year-old Chinese male developed severe aregenerative anemia. The bone marrow was diffusely hypercellular with increased marrow reticulin and a persistent failure of erythroid differentiation beyond the pronormoblast stage. Although he did not manifest classic features of systemic lupus erythematosus, multiple serologic studies were in accord with this diagnosis. The patient's defect in erythropoiesis was studied by an in vitro technique for the growth of erythroid colonies. Despite the severe erythroid hypoplasia, the patient's marrow yielded abundant large erythroid colonies. Serum erythropoietin activity was high as judged by use of this in vitro assay. Although the patient's native serum did not affect colony formation, a separated IgG fraction was markedly inhibitory to colony growth. This suggests that the erythroid hypoplasia may have resulted from a unique autoantibody. The patient's hematologic abnormalities completely reversed following treatment with corticosteroids.

Topics: Adrenal Cortex Hormones; Adult; Anemia, Aplastic; Bone Marrow; Colony-Forming Units Assay; Erythropoiesis; Erythropoietin; Humans; Immunoglobulin G; Lupus Erythematosus, Systemic; Male; Reticulin

Topics: Adult; Anemia, Sideroblastic; Bone Marrow Cells; Bone Marrow Examination; Erythropoiesis; Erythropoietin; Exchange Transfusion, Whole Blood; Folic Acid; Humans; Iron; Isoniazid; Lupus Erythematosus, Systemic; Male; Megakaryocytes; Prednisone; Proteinuria; Pyridoxine; Vitamin B 12