mycophenolic-acid and Agammaglobulinemia

Secondary hypogammaglobulinemia after heart transplantation may follow immunosuppressive therapy with the resultant increased risk of infections, including cytomegalovirus (CMV) disease. There is limited information on the use of intravenous immunoglobulin replacement therapy (IVIG) in heart-transplanted patients with hypogammaglobulinemia and CMV disease. We present data on five consecutive heart-transplanted patients with relapsing CMV disease, four of whom developed gastrointestinal disease. The immunosuppressive regimen included prednisone, cyclosporine A, azathioprine, mycophenolate mofetil, tacrolimus and antithymocyte globulin (ATG). Evaluation revealed CMV antigenemia. All the patients had been treated with intravenous ganciclovir. In addition, hyperimmune CMV immunoglobulin was administered in three patients. Significantly reduced levels of immunoglobulin G (IgG) were observed in the patients as compared with 15 heart-transplanted individuals without CMV disease [mean IgG levels: 323+/-18 and 639+/-63 mg/dl, respectively (p=0.003)]. IVIG [FLEBOGAMMA], 200-400 mg/kg every 21 days with the goal of maintaining normal serum IgG levels, was added for the treatment of CMV disease. Selected batches with the highest anti-CMV titers were set apart for the treatment of the patients. IVIG treatment, in combination with antiviral therapy, proved able to control CMV disease. There was a favorable clinical response and the patients became free of gastrointestinal symptoms. Detection of CMV antigens was negative after treatment. During IVIG therapy no immediate or delayed adverse effects were observed. Even if our survey was limited to five cases, the results suggest that addition of IVIG to antiviral chemotherapy might improve outcome in heart-transplanted patients with hypogammaglobulinemia and CMV disease.

Topics: Agammaglobulinemia; Antilymphocyte Serum; Antiviral Agents; Azathioprine; Cyclosporine; Cytomegalovirus Infections; Drug Therapy, Combination; Female; Ganciclovir; Heart Transplantation; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins, Intravenous; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Prednisone; Recurrence; Tacrolimus

Mycophenolate mofetil (MMF) is an immunosuppressive drug used for the treatment of autoimmune rheumatological diseases. To test the risk of hypothetical drug-induced hypogammaglobulinemia, the aim of this study was to report the trend of the immunoglobulin (Ig) values and of the infectious diseases in children treated with MMF. This study retrospectively evaluated demographic, clinical, and laboratory data of a cohort of patients affected by a chronic rheumatic disease receiving MMF, followed at the Rheumatology Unit of Meyer Children Hospital, Florence. A total of 29 pediatric patients were enrolled. In patients with normal values of immunoglobulins at the baseline, treatment with MMF resulted in a statistically significant reduction of the IgG levels (p = 0.0058) and in a decrease of IgM levels not reaching statistical significance. The levels of IgA were not affected. During the follow-up, seven patients developed an humoral immune defect. The univariate analysis did not identify any risk factors related to the iatrogenic hypogammaglobulinemia. The infection rate during MMF therapy was significantly higher than the 12-month period before therapy (p = 0.006), while the severe infections did not significantly increase (p = 0.1818), even considering only the patients with hypogammaglobulinemia.. In pediatric patients with chronic rheumatic diseases, immunological first level tests and serological analyses to screen the protection against the common childhood pathogens are suggested before starting an immunosuppressive drug. These patients should also complete the vaccination schedule. In patients treated with MMF a strict monitoring of Ig is required during treatment and after discontinuation of the drug.. • MMF is an immunosuppressive drug initially used for the treatment of the graft-versus-host disease. • Mycophenolic acid is an inhibitor of inosine-5'-monophosphate dehydrogenase, expressed in lymphocytes; therefore, MMF could impair the immune system function.. • MMF resulted in a reduction of IgG and an increase of not severe infection rate. • Immunological first level tests, including Ig, lymphocyte subpopulations, and antibody response to vaccines, are suggested in pediatric patients before starting MMF; a strict monitoring of Ig is important before, during, and after MMF treatment.

Topics: Agammaglobulinemia; Child; Disease Susceptibility; Humans; Immunoglobulin G; Immunosuppressive Agents; Mycophenolic Acid; Retrospective Studies

Topics: Adolescent; Agammaglobulinemia; Child; Humans; Immunologic Factors; Mycophenolic Acid; Nephrotic Syndrome; Rituximab

X-linked agammaglobulinemia (XLA) diagnosed in the first year of life is an immunodeficiency with a life-long indication for substitution of immunoglobulins, due to lack of B lymphocytes in the periphery. The decrease of bacterial infection frequency and severity is an effect of immunoglobulin replacement. However, in the majority of patients bronchiectasis and chronic sinusitis with an overgrown mucous membrane develop despite regular substitution. Autoimmune diseases as co-existing diseases in XLA are noted in a few patients presenting symptoms associated with arthritis, scleroderma and myositis. Our patient was diagnosed with XLA in the first year of life, followed by regular substitution of immunoglobulins. The symptoms of pain, edema of muscles of the right shank with skin edema and discoloration after mild injury were noted in a 13-year-old boy. Shulman disease was diagnosed after 6 months of symptoms, based on histopathology of muscle and skin biopsy. Before the diagnosis, non-steroid anti-inflammatory drugs (NSAID) were used with a transient effect. After the diagnosis, therapy included steroids, immunoglobulins in a high dose and immunosuppression, with improvement of clinical symptoms. During methotrexate (MTX) therapy the patient developed two episodes of pneumonia, so mycophenolate mofetil (MMF) was used, with a similar effect. Now, with this therapy, the symptoms are mild and stable without progression.

Topics: Adolescent; Agammaglobulinemia; Antibiotics, Antineoplastic; Eosinophilia; Fasciitis; Genetic Diseases, X-Linked; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid

Bronchiectasis is characterized by abnormal, permanent and irreversible dilatation of the bronchi, usually responsible for daily symptoms and frequent respiratory complications. Many causes have been identified, but only limited data are available concerning the association between bronchiectasis and renal transplantation.. We conducted a retrospective multicenter study of cases of bronchiectasis diagnosed after renal transplantation in 14 renal transplantation departments (French SPIESSER group). Demographic, clinical, laboratory and CT scan data were collected.. Forty-six patients were included (mean age 58.2 years, 52.2 % men). Autosomal dominant polycystic kidney disease (32.6 %) was the main underlying renal disease. Chronic cough and sputum (50.0 %) were the major symptoms leading to chest CT scan. Mean duration of symptoms before diagnosis was 1.5 years [0-12.1 years]. Microorganisms were identified in 22 patients, predominantly Haemophilus influenzae. Hypogammaglobulinemia was observed in 46.9 % patients. Bronchiectasis was usually extensive (84.8 %). The total bronchiectasis score was 7.4 ± 5.5 with a significant gradient from apex to bases. Many patients remained symptomatic (43.5 %) and/or presented recurrent respiratory tract infections (37.0 %) during follow-up. Six deaths (13 %) occurred during follow-up, but none were attributable to bronchiectasis.. These results highlight that the diagnosis of bronchiectasis should be considered in patients with de novo respiratory symptoms after renal transplantation. Further studies are needed to more clearly understand the mechanisms underlying bronchiectasis in this setting.

Topics: Adult; Agammaglobulinemia; Aged; Aged, 80 and over; Azathioprine; Bronchiectasis; Chronic Disease; Cough; Cyclosporine; Everolimus; Female; Forced Expiratory Volume; Graft Rejection; Haemophilus Infections; Haemophilus influenzae; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Polycystic Kidney, Autosomal Dominant; Respiratory Tract Infections; Retrospective Studies; Risk Factors; Rituximab; Sirolimus; Tacrolimus; Tomography, X-Ray Computed; Vital Capacity; Young Adult

Several studies have suggested an association between post-transplant immunoglobulin (Ig) levels and the development of infection in solid organ transplantation. We therefore conducted exploratory analyses of potential factors associated with bacterial infection/sepsis after living-donor liver transplantation (LDLT).. Blood samples from 177 recipients who received primary LDLT between September 1999 and November 2011 were available for study. Hypogammaglobulinemia was defined as having at least 1 IgG level <650 mg/dL within 7 days after LDLT. Risk factors for developing post-transplant bacterial infection and sepsis within 3 months after LDLT were analyzed.. Fifty (28.2%) recipients experienced bacterial infection within 3 months of LDLT. Eighty-four (47.5%) recipients had hypogammaglobulinemia, although no recipients had hypogammaglobulinemia before LDLT. Hypogammaglobulinemia, undergoing hepaticojejunostomy, and portal pressure at closure >15 mmHg were independent risk factors for developing bacterial infection within 3 months of LDLT (P < 0.0001 P = 0.0008, and P = 0.011, respectively). The odds ratio (OR) and confidence interval (CI) for hypogammaglobulinemia were 4.79 and 2.27-10.7, respectively. Twenty-four (13.6%) recipients developed bacterial sepsis within 3 months. Hypogammaglobulinemia, operative time >14 h, model for end-stage liver disease score >15, and no mycophenolate mofetil use were independent risk factors for developing bacterial sepsis (P = 0.009, P = 0.001, P = 0.003, and P = 0.005, respectively). The OR and CI for hypogammaglobulinemia were 3.83 and 1.38-12.0, respectively.. Hypogammaglobulinemia within 7 days of LDLT was a significant risk factor for post-transplant bacterial infection and sepsis.

Topics: Adult; Agammaglobulinemia; Anastomosis, Surgical; Bacterial Infections; End Stage Liver Disease; Female; Hepatic Duct, Common; Humans; Hypertension, Portal; Immunoglobulin G; Immunosuppressive Agents; Jejunum; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Operative Time; Retrospective Studies; Risk Factors; Sepsis; Severity of Illness Index; Time Factors

X-linked agammaglobulinaemia (XLA) is the most common inherited humoural immunodeficiency disorder. Mutations in the gene coding for Bruton's tyrosine kinase (BTK) have been identified as the cause of XLA. Most affected patients exhibit a marked reduction of serum immunoglobulins, mature B cells, and an increased susceptibility to recurrent bacterial infections. However, the diagnosis of XLA can be a challenge in certain patients who have near-normal levels of serum immunoglobulin. Furthermore, reports on XLA with renal involvement are scant.. We report an atypical XLA patient who presented with selective immunoglobulin M (IgM) immunodeficiency and nephropathy. He was diagnosed with selective IgM immunodeficiency, based on his normal serum immunoglobulin G (IgG) and immunoglobulin A (IgA) levels but undetectable serum IgM level. Intravenous immunoglobulin was initiated due to increased infections and persistent proteinuria but no improvement in proteinuria was found. A lupus-like nephritis was detected in his kidney biopsy and the proteinuria subsided after receiving a mycophenolate mofetil regimen. Although he had a history of recurrent bacterial infections since childhood, XLA was not diagnosed until B-lymphocyte surface antigen studies and a genetic analysis were conducted.. We suggest that B-lymphocyte surface antigen studies and a BTK mutation analysis should be performed in familial patients with selective IgM deficiency to rule out atypical XLA.

Topics: Agammaglobulinemia; Antigens, Differentiation, B-Lymphocyte; Child; Genetic Diseases, X-Linked; Humans; Immunoglobulin M; Male; Mycophenolic Acid; Nephritis; Proteinuria

The authors report on a 55-year-old female patient after R1 resection of a malignant thymoma with spindle type epithelial cells (WHO type A, Masaoka stage III) referred for further therapy of an ulcerative colitis. At that time, both adjuvant radiation and cytostatic therapy were not applicable due to severe activity of the ulcerative colitis. Under immunosuppressive treatment with azathioprine and steroids, the patient developed cytomegalovirus (CMV) enteritis which was triggered by therapy-induced leukopenia. After a switch from azathioprine to mycophenolatmofetil (MMF) treatment and administration of cidofovir because of nonresponse to ganciclovir and incompatibility of foscarnet sodium (Foscavir), the patient clinically improved. In addition, the patient was treated with immunoglobulins every 3-4 weeks because of antibody deficiency. At present, 3.5 years after R1 resection, the patient still has no clues of a remaining tumor mass under current immunosuppressive therapy. Ulcerative colitis is also in complete remission stage.. This case indicates the very rare features of a syndrome with thymoma and antibody deficiency which was first described by Robert Good. Furthermore, the impact of immunosuppressive therapy and management of opportunistic infections on the course of this disease is obvious.

Topics: Agammaglobulinemia; Antiviral Agents; Azathioprine; Cidofovir; Colitis, Ulcerative; Cytomegalovirus Infections; Cytosine; Enteritis; Female; Humans; Immunization, Passive; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Leukopenia; Middle Aged; Mycophenolic Acid; Neoplasm Staging; Opportunistic Infections; Organophosphonates; Postoperative Complications; Syndrome; Thymectomy; Thymoma; Thymus Neoplasms