lactoferrin and Autoimmune-Diseases

The present review is focused on the clinical significance of lactoferrin in pancreatic secretions and stone formation in chronic pancreatitis, and of serum anti-lactoferrin antibody in autoimmune pancreatitis. Lactoferrin secretion is increased in pancreatic secretions in calcified and non-calcified chronic pancreatitis. Lactoferrin, pancreatic stone protein and trypsin are present in pancreatic stones. We cannot conclude which protein is more important for the precipitate and stone formation. The presence of antilactoferrin antibody has been reported in serum in autoimmune diseases, such as autoimmune pancreatitis. The coincidental appearance of autoimmune pancreatitis with extrapancreatic autoimmune diseases strongly suggests a common autoimmune mechanism and lactoferrin is a candidate antigen. Lactoferrin may play an important role as a precipitate protein in pancreatic stone formation in chronic pancreatitis and as an autoantigen in autoimmune pancreatitis. Further studies are required to better understand the role of lactoferrin.

Topics: Autoantibodies; Autoantigens; Autoimmune Diseases; Humans; Lactoferrin; Lithiasis; Pancreatitis, Chronic

Autoimmune pancreatitis (AIP) is a new clinical entity recently described. Histologically it consists of a lymphoplasmacytic infiltration with diffuse fibrosis. Pancreatic imaging on US, CT and ERCP shows diffuse enlargement of the pancreatic gland and an irregular narrowing of the pancreatic duct. Hypergammaglobulinemia, increased serum levels of total IgG or IgG4, positive antilactoferrin and anti carbonic anhydrase II autoantibodies are quite frequently found in autoimmune pancreatitis. Laboratory data, pancreatic images and diabetes mellitus improve under oral steroid therapy.

Topics: Age of Onset; Autoantibodies; Autoimmune Diseases; Carbonic Anhydrase II; Cholangiopancreatography, Endoscopic Retrograde; Female; Humans; Hypergammaglobulinemia; Lactoferrin; Male; Middle Aged; Pancreas; Pancreatitis, Chronic; Steroids

Colostrum and milk are rich in proteins and peptides which play a crucial role in innate immunity when transferred to the offspring and may accelerate maturation of the immune system in neonates. The immunotropic properties of these proteins prompted investigators research their potential application in prevention and therapy. Lactoferrin (LF) exhibits antibacterial, antifungal, antiviral, antiparasitice, and antitumoral activities. It is protective with regard to intestinal epithelium, promotes bone growth, and accelerates the recovery of immune system function in immunocompromised animals. LF was tried in the treatment of hepatitis C infection and the intestinal form of graft-versus-host disease (GvHD). A proline-rich polypeptide (PRP) demonstrated a variety of immunotropic functions, including the promotion of T-cell maturation and inhibition of autoimmune disorders. PRP, in the form of chewable tablets (Colostrinin) was recently found to improve or stabilize the health status of Alzheimer's disease patients. Casein and casein-derived peptides showed protective activities in enamel demineralization and as caries-preventing agents. The protein hydrolyzates were also protective in diabetic animals, reduced tumor growth, had antihypertensive activity and diminished colicky symptoms in infants. Glycomacropeptide (GMP), a peptide derived from kappa-casein, exhibited various antibacterial and antithrombotic activities. Alpha-lactalbumin (LA) demonstrated antiviral, antitumoral and anti-stress properties. LA-enriched diets were anxiolytic, lowered blood pressure in rats, prevented diarrhea, and led to a better weight gain in malnourished children. HAMLET, a complex of LA and oleic acid, was effective in patients with cutaneous papillomas. Lysozyme found application in infant formulas, the treatment of periodentitis, and the prevention of tooth decay. Milk enriched in lysozyme was used in feeding premature infants suffering from concomitant diseases. Interesting, antibacterial properties were exhibited by lactoperoxidase. Both lysozyme and lactoperoxidase required cooperative action with LF in combating bacteria. In conclusion, preparations derived from milk and colostrum are effective, easily bioaccessible, and safe, finding wide application in prevention and therapy for newborns and adults.

Topics: Adult; Alzheimer Disease; Animals; Anti-Infective Agents; Antineoplastic Agents; Autoimmune Diseases; Caseins; Child; Colostrum; Female; Humans; Infant; Infant, Newborn; Intercellular Signaling Peptides and Proteins; Lactoferrin; Lactoperoxidase; Malnutrition; Milk Proteins; Neoplasms; Peptides; Pregnancy; Tooth Diseases

New cysteine protease inhibitors in human tears and milk and their medical significance are reviewed in this paper. As protective components against bacterial infection in the eyes, we detected four kinds of anti-bacterial proteins in normal human tears including lysozyme and three kinds of cysteine protease inhibitors. Using our reverse zymography of normal tears, three kinds of cysteine protease inhibitors were found to be 78kDa, 20kDa and 15kDa and were determined to be lactoferrin, Von Ebner's Gland (VEG) protein and cystatin S, respectively. All of them belong to the cystatin super family and VEG protein and cystatin S are well known cysteine protease inhibitors. The C-terminus area 17mer peptide, Y679-K695, of lactoferrin showed strong homology with a common active domain of the cystatin family and the synthesized peptide showed inhibition of cysteine proteases. Not only were disease-specific changes found in these inhibitor profiles, but also disease-specific new inhibitors in patients tears with certain autoimmune diseases. A 35kDa inhibitor, which was detected specifically in tears with Behcet's disease, an typical autoimmune disease, was determined to be a lacrimal acidic proline-rich protein based on the N-terminus sequence analysis. A 65kDa inhibitor of tears with Harada's autoimmune disease was determined to be an Ig heavy chain V-III region. In addition, lactoferrin content in Harada's disease was very low. We found two cathepsin inhibitors in bovine milk using reverse zymography, namely lactoferrin and beta-casein. The L133-Q151, in the human beta-casein molecule is the active inhibitory domain. They may play an important role in antiseptic and anti-infectious functions.

Topics: Animals; Autoimmune Diseases; Bacteria; Bacterial Infections; Caseins; Cattle; Clinical Enzyme Tests; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Humans; Lactoferrin; Milk; Molecular Weight; Tears

Secretory lactoferrins play a crucial rolls at mucosal surfaces as not only antimicrobial molecules in primate as well as human, but as physiological protein. Its multiple functions extended to be one of immunogen could elicited autoimmune disorders. Purified camel lactoferrin (cLfs) from different Saudi camel clans were shown to be a potent immunogen when injected into rabbit. Four rabbit were subcutaneously immunized with different camel clans lactoferrin/Freunds adjuvant. Anti-cLfs potency titration was reach 1:32000 and did not significantly differences between different cLfs. The cross-reactivity level of different anti-Lfs were highly significant, specially between cLfs and bLf/hLf.

Topics: Animals; Anti-Infective Agents; Antibody Formation; Autoimmune Diseases; Camelus; Cattle; Cross Reactions; Humans; Lactoferrin; Milk; Rabbits; Saudi Arabia

To study the autoimmune response in MRL/Mp mice, which spontaneously develop pancreatitis in the exocrine pancreatic tissue.. Six-week-old female mice were injected intraperitoneally with polyinosinic polycytidylic acid at a dose of 5 mg/kg of body weight twice a week for up to 12 weeks. The mice were serially killed, and the severity of their pancreatitis was graded with a histological scoring system. Immunohistological examinations were performed, and the serum levels of autoantibodies were measured by enzyme-linked immunosorbent assay.. The administration of polyinosinic polycytidylic acid accelerated the development of pancreatitis, with abundant infiltration of B220 B cells and CD138 plasmacytes. Various autoantibodies directed against autoantigens, including carbonic anhydrase II and lactoferrin, were detected but none against glutamic acid decarboxylase. Of these, autoantibodies directed against the pancreatic secretory trypsin inhibitor (PSTI; 91.7%) were more prevalent than those against carbonic anhydrase II (33.3%) or lactoferrin (45.8%). Determination of the epitope of the anti-PSTI antibody showed that most immunoreactivity was directed at the site on PSTI that is active in the suppression of trypsin activity.. The autoimmune response to PSTI protein may induce a failure of PSTI activity, resulting in the activation of trypsinogen and the subsequent disease progression.

Topics: Animals; Autoantibodies; Autoimmune Diseases; B-Lymphocytes; Carbonic Anhydrase II; Disease Models, Animal; Disease Progression; Enzyme-Linked Immunosorbent Assay; Epitope Mapping; Female; Immunity, Humoral; Immunoglobulin G; Immunohistochemistry; Lactoferrin; Leukocyte Common Antigens; Mice; Mice, Inbred C57BL; Pancreas; Pancreatitis; Plasma Cells; Poly I-C; Syndecan-1; Trypsin Inhibitor, Kazal Pancreatic

Although autoimmune pancreatitis (AIP) has been recently recognized as a new disease entity of chronic pancreatitis, the clinical diagnosis of the disease remains disputed. Autoantibodies against carbonic anhydrase II and lactoferrin are detected in most patients with AIP, but not in about 10%. We undertook this study to determine whether additional autoantibodies are present in the serum level of AIP patients.. We recruited 26 patients with AIP for the study. For comparison, we also recruited 53 patients with various pancreatic diseases and 12 healthy subjects. We immunoscreened human pancreatic cDNA library using patients' sera. Positive clones were analyzed by DNA sequencing and were constructed into a pGEX-4T-1 expression vector. The recombinant proteins were used as antigens in enzyme-linked immunosorbent assay to screen the subjects' sera for autoantibodies.. We cloned a cDNA encoding the pancreatic secretory trypsin inhibitor (PSTI). Among 26 patients with AIP, autoantibodies against PSTI were significantly positive in 11 (42.3%) by western blotting and in 8 (30.8%) by enzyme-linked immunosorbent assay, respectively. However, none of control subjects was positive for anti-PSTI antibodies.. These findings suggest that PSTI may be related to the pathogenesis of AIP, and autoantibodies against PSTI can be a useful diagnostic marker for the disease.

Topics: Aged; Autoantibodies; Autoimmune Diseases; Biomarkers; Carbonic Anhydrase II; Cloning, Molecular; Enzyme-Linked Immunosorbent Assay; Female; Glutathione Transferase; Humans; Lactoferrin; Male; Middle Aged; Pancreatitis, Chronic; Recombinant Fusion Proteins; Trypsin Inhibitor, Kazal Pancreatic

We analysed and compared electrophoretic tear proteins patterns of healthy subjects and patients with different autoimmune diseases associated with secondary Sjogren's syndrome.. Tears were collected using the Schirmer's method. Proteins were separated by sodium-dodecyl sulfate polyacrylamide gel electrophoresis. The lanes were stained by Coomassie blue and/or silver.. Lactoferrin, albumin, lipocalin and lysozyme were found to be the main components being identified using molecular weight markers.. Electrophoretic analysis of tear proteins patterns is a fast, reproducible and simple method which provides information about the possibility of lacrimal gland involvement in auto-immune diseases.

Topics: Anti-Infective Agents; Autoimmune Diseases; Carrier Proteins; Cysteine Proteinase Inhibitors; Electrophoresis, Gel, Two-Dimensional; Eye Proteins; Humans; Lactoferrin; Lipocalin 1; Muramidase; Sjogren's Syndrome; Tears

We analysed and compared electrophoretic tear protein patterns of healthy subjects and patients with different autoimmune diseases associated with secondary Sjogren's syndrome.. Tears were collected using the Schirmer's method. Proteins were separated by sodium-dodecyl sulfate poliacrylamide gel electrophoresis. The lanes were stained by Coomassie blue and/or silver.. Lactoferrin, albumin, lipocalin and lysozyme were found to be the main components being identified using molecular weight markers.. Electrophoretic analysis of tear proteins patterns is a fast, reproducible and simple method which provides information about the possibility of lacrimal gland involvement in autoimmmune diseases.

Topics: Albumins; Anti-Infective Agents; Autoimmune Diseases; Carrier Proteins; Case-Control Studies; Electrophoresis, Polyacrylamide Gel; Eye Proteins; Humans; Lactoferrin; Lipocalin 1; Muramidase; Sensitivity and Specificity; Sjogren's Syndrome; Tears

Topics: Adult; Alleles; Antibody Specificity; Autoantibodies; Autoantigens; Autoimmune Diseases; Carbonic Anhydrase II; Diabetes Mellitus, Type 1; Female; Genes, MHC Class II; Genetic Predisposition to Disease; Glutamate Decarboxylase; HLA Antigens; HLA-DQ Antigens; HLA-DQ beta-Chains; HLA-DR Antigens; HLA-DRB1 Chains; Humans; Islets of Langerhans; Japan; Lactoferrin; Male; Membrane Proteins; Middle Aged; Pancreas, Exocrine; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases; Receptor-Like Protein Tyrosine Phosphatases, Class 8

We previously reported that autoantibodies against carbonic anhydrase II and lactoferrin are frequently identified in patients with autoimmune-related pancreatitis. To clarify the role of carbonic anhydrase II and lactoferrin, we created animal models of autoimmune pancreatitis by immunizing neonatally thymectomized mice with carbonic anhydrase II and lactoferrin and also by transferring immunized spleen cells to nude mice. Neonatally thymectomized BALB/c mice were immunized with carbonic anhydrase II or lactoferrin followed by three booster injections (n = 10 in each group). We transferred whole, CD4+, or CD8+ spleen cells prepared from immunized neonatally thymectomized mice to nude mice (n = 5 in each group). Gene expression of IFN-gamma and IL-4 was investigated using semiquantitative reverse transcription-polymerase chain reaction. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining was used to examine apoptosis. In immunized neonatally thymectomized mice, the prevalence of inflammation was significantly higher in the pancreas. Inflammation was present in all mice receiving whole or CD4+ cells. There was no change in any of the mice receiving CD8+ cells or nonimmunized spleen cells. Carbonic anhydrase II or lactoferrin-immunized mice had apoptotic duct cells or acinar cells, respectively. Expression of the IFN-gamma gene was up-regulated in each group. Similar findings were observed in the salivary glands and liver. An immunologic mechanism against carbonic anhydrase II or lactoferrin is involved in the pathogenesis of these pancreatitis models, in which the effector cells are Th1-type CD4+ T cells.

Topics: Adoptive Transfer; Animals; Autoimmune Diseases; Carbonic Anhydrase II; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Disease Models, Animal; Female; Gene Expression; Immunization; In Situ Nick-End Labeling; Interferon-gamma; Interleukin-4; Lactoferrin; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Pancreas; Pancreatitis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Salivary Glands; Spleen; Thymectomy

Although autoimmunity may be involved in some cases of pancreatitis, the mechanism is still unknown. To clarify this, we studied serum autoantibodies, subsets of lymphocytes, and the Th1/Th2 balance of cellular immune responses in patients with autoimmune-related pancreatitis (AIP).. Seventeen patients with AIP (8 men and 9 women; age, 53.2 +/- 13.0 years) were studied. Autoantibodies including antilactoferrin (ALF) or carbonic anhydrase II antibody (ACA-II) were examined using the enzyme-linked immunosorbent assay (ELISA) or the indirect fluorescein antibody method. Intracellular cytokines (interferon gamma and interleukin 4) and subtypes of peripheral blood lymphocytes were examined by flow cytometry and ELISA.. More than one autoantibody was observed in all 17 patients. Serum antinuclear antibody was detected in 13 of 17 patients, ALF antibody in 13, ACA-II antibody in 10, rheumatoid factor in 5, and anti-smooth muscle antibody in 3, but antimitochondrial antibody in none. The serum levels of ACA-II and LF antibody were not correlated. HLA-DR(+)CD8(+) and HLA-DR(+)CD4(+) cells were significantly increased in peripheral blood (P < 0.05). CD4(+) cells producing interferon gamma and the secreted levels were significantly increased compared with those in controls (P < 0.05), but interleukin 4 was not increased.. An autoimmune mechanism against CA-II or LF, and Th1-type immune response, may be involved in AIP.

Topics: Adult; Aged; Antibody Formation; Autoantibodies; Autoimmune Diseases; Carbonic Anhydrases; Cytokines; Female; Humans; Lactoferrin; Lymphocyte Subsets; Male; Middle Aged; Pancreatitis; Th1 Cells; Th2 Cells

To investigate the prevalence and clinical relevance of immunoglobulin (Ig) isotypes of antimyeloperoxidase (MPO) and antilactoferrin (LF) antibodies in collagen diseases, enzyme-linked immunosorbent assay was employed to detect the Ig isotypes of both antibodies. The purified proteins of MPO and LF were used as two major representative antigens for anti-neutrophil cytoplasmic antibodies (ANCA) with a perinuclear staining pattern by an indirect immunofluorescent technique. We examined 131 serum samples from 79 patients with rheumatoid arthritis (RA), 32 with systemic lupus erythematosus (SLE), 14 with progressive systemic sclerosis (PSS), 6 with polymyositis/dermatomyositis (PM/DM), and 5 with idiopathic crescentic glomerulonephritis who served as positive controls and 36 healthy subjects who served as controls. A limited number of patients with RA (4-10%), SLE (6-9%), and PSS (7-14%) but not PM/DM showed positive IgG or IgA anti-MPO antibody (MPO-ANCA) but not IgM MPO-ANCA. However, 10-20% of RA, 40-60% of SLE, 20-36% of PSS but none of the PM/DM patients showed positive IgG, IgA, or IgM anti-LF antibody (LF-ANCA). MPO- and LF-ANCA positivity in RA patients was correlated with markers of disease activity such as the erythrocyte sedimentation rate, C-reactive protein, and serum Ig levels. IgG LF-ANCA but not MPO-ANCA positivity in SLE patients also was correlated with the disease activity index but not with clinical features. Neither MPO- nor LF-ANCA positivity in PSS patients was correlated with any clinical features. Overall, both MPO- and LF-ANCA were found mainly in RA, SLE, and PSS patients but not in PM/DM patients. The Ig isotypes of MPO- and LF-ANCA frequently belonged to both IgG and IgA and rarely to the IgM class. Both MPO- and LF-ANCA positivity reflected disease activity in RA and SLE rather than specific organ involvement.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Antineutrophil Cytoplasmic; Antibody Specificity; Arthritis, Rheumatoid; Autoantigens; Autoimmune Diseases; Collagen Diseases; Dermatomyositis; Enzyme-Linked Immunosorbent Assay; Female; Glomerulonephritis; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin Isotypes; Immunoglobulin M; Lactoferrin; Lupus Erythematosus, Systemic; Male; Middle Aged; Organ Specificity; Peroxidase; Polymyositis; Scleroderma, Systemic

Several investigators have reported on autoimmune-related pancreatitis, but the clinical findings and pathophysiology still remain unclear. To clarify it, we analyzed eight patients with autoimmune pancreatitis.. We evaluated clinical findings in eight patients (four men and four women) with autoimmune-related pancreatitis. Patients were aged 45-73 yr (mean, 57.5 yr). We examined blood chemistry and immunological studies, including autoantibodies against lactoferrin or carbonic anhydrase II, and compared ERCP images with clinical findings. In two patients, we studied the subset of lymphocytes infiltrating in the pancreas by immunohistochemistry and flow cytometry.. Four of eight patients had jaundice, two had renal dysfunction, two had abdominal pain, and two had back pain. Three patients were complicated with other autoimmune diseases. Three patients showed abnormal pancreatic exocrine function by an N-benzoyl-L-tyrosyl-para-aminobenzoic acid excretion test. Antinuclear antibody was detected in four of eight patients, antilactoferrin antibody in three of six, anticarbonic anhydrase II antibody in two of six, antismooth muscle antibody in two of seven, and rheumatoid factor in one of eight. All eight patients showed segmental stenosis of the main pancreatic duct by ERCP. Four patients showed stenosis of the common bile duct as well as the pancreatic duct. Microscopic findings showed infiltration of CD4-positive lymphocytes around the pancreatic duct, and HLA-DR was expressed on both CD4-positive cells and pancreatic duct cells. In two patients, stenosis of the pancreatic duct improved by prednisolone.. Autoimmune mechanism may be involved in some patients with idiopathic pancreatitis associated with hypergammaglobulinemia.

Topics: Aged; Autoantibodies; Autoimmune Diseases; Carbonic Anhydrases; Cholangiopancreatography, Endoscopic Retrograde; Female; Flow Cytometry; Humans; Hypergammaglobulinemia; Lactoferrin; Lymphocyte Subsets; Male; Middle Aged; Pancreas; Pancreatitis

Lactoferrin, an immunoregulatory protein in mucosal secretions, is one of the target antigens to perinuclear antineutrophil cytoplasmic antibodies (P-ANCAs). Circulating lactoferrin is cleared in the liver, but little is known about the implication of lactoferrin in hepatic inflammation. To evaluate the implication of immunological response to lactoferrin, we examined antilactoferrin antibodies in autoimmune liver diseases.. Fourteen patients with primary biliary cirrhosis (PBC), 14 with autoimmune hepatitis (AIH), five with autoimmune cholangitis (AIC), six with chronic hepatitis C, and five with chronic hepatitis B were studied. We evaluated autoantibodies to lactoferrin in the sera of the patients by the Western Immunoblotting method.. Sera of five of the 14 patients (35.7%) with PBC, four of the 14 patients (28.6%) with AIH, and five of the five patients (100%) with AIC contained autoantibodies to human lactoferrin, but none with hepatitis B or C had them. The higher prevalence of serum antibodies to human lactoferrin was shown to be higher in patients with AIC than with hepatitis B (p < 0.01), hepatitis C (p < 0.01), PBC (p < 0.05), and AIH (p < 0.05).. Lactoferrin located in bile ducts and liver cells is one of the candidates of target antigens in autoimmune liver diseases, especially in AIC.

Topics: Adolescent; Adult; Aged; Autoantibodies; Autoimmune Diseases; Blotting, Western; Chi-Square Distribution; Electrophoresis, Polyacrylamide Gel; Female; Humans; Lactoferrin; Liver Diseases; Male; Middle Aged; Statistics, Nonparametric

Topics: Autoantibodies; Autoantigens; Autoimmune Diseases; Child; Child, Preschool; Humans; Infant; Lactoferrin; Milk Hypersensitivity

Phagocytic number (PN) and phagocytic index (PI) of neutrophils isolated from blood of patients with autoimmune diseases, allergy to Staphylococcus aureus and from blood of healthy individuals were examined. Our results concerning the influence of lactoferrin (Lf); (6.7 mg/l) on the PI of PMN showed that: 1) Lf enhances reliable PI of PMN at the 30-th minute starting the phagocytic reaction in patients with autoimmune disease in an active stage, in blood donors treated as healthy with the presence of autoantibodies, in patients with autoimmune diseases and proved autoantibodies against tissue, cell antigens and collagen, 2) Lf influences non-significantly PI of PMN in patients with autoimmune collagen diseases in remission, 3) Lf increases PI of PMN with 19% only in 58% from the assessed patients with Staphylococcus aureus, and 4) Lf decreases non-significantly PI of PMN in the healthy controls. Our studies on the effect of Lf on the phagocytic activity of PMN suggest that Lf has stronger effect on the PN compared to the PI: 1) Lf enhances with 86% the PN in patients with Staphylococcus aureus, 2) Lf increases PN of PMN in all of the assessed patients with autoimmune collagen diseases in active stage (mean with 72%), and 3) Lf increases PN of PMN in 4 from the 5 investigated healthy controls (mean with 22%). Our results show a "corrective" effect of Lf on the phagocytic functions in the investigated groups of patients. The possible mechanisms, by which Lf increases PN and PI of neutrophils, is discussed: 1) they may concern the antioxidative properties of Lf to block the iron ions in their catalytic inactive form or to take part as ferric-Lf in an oxidative-reduction processes on the plasma membrane and controlling transmembrane transport systems, 2) Lf decreases the negative surface charge and thus enhances the adherent ability of the PMN. Probably to this stimulated adherent ability dues the increased ingestion of bacteria in the presence of Lf, and 3) The "changed" membrane of PMN may have higher number receptors for Lf to bind more molecules of exogenous Lf. The increase of Lf binding which enhances the adherence and aggregation of neutrophils, facilitates the phagocytosis.

Topics: Adolescent; Adult; Antigens, Bacterial; Autoimmune Diseases; Humans; Hypersensitivity; Lactoferrin; Lymphocyte Activation; Male; Neutrophils; Phagocytosis; Staphylococcus aureus

Topics: Adult; Animals; Antibodies; Antibody Formation; Autoimmune Diseases; Breast Feeding; Carbohydrate Metabolism, Inborn Errors; Cattle; Failure to Thrive; Female; Gambia; Humans; Infant, Newborn; Lactoferrin; Milk; Reference Values; Sweden

Topics: Autoantibodies; Autoimmune Diseases; Cholangitis, Sclerosing; Colitis, Ulcerative; Humans; Lactoferrin; Neutrophils

We document here by Western immunoblotting and immunogold ultracytochemistry that polyclonal antibodies against human lactoferrin (Lf) bind to tubercle and leprosy bacilli. In situ immunogold labeling of Mycobacterium leprae (present in armadillo liver and in human skin) and of Mycobacterium tuberculosis indicated that receptors for anti-Lf antibodies were present both on the cytoplasm and on the envelope of the bacilli. We found by immunoblotting that the 65-kDa heat shock protein is the major component of M. leprae and M. tuberculosis that is responsible for the binding of the anti-Lf probe. Furthermore, we show that anti-Lf immunoglobulin G eluted from the nitrocellulose-transferred mycobacterial 65-kDa protein band did bind back to Lf. Ultracytochemistry of biopsy samples of human lepromas showed that dead or severely damaged M. leprae was strongly marked by the anti-Lf antibodies; a similar pattern of immunogold marking was observed on M. leprae when antibodies against the 65-kDa mycobacterial protein were used. Our results offer direct evidence that the 65-kDa protein of leprosy and tubercle bacilli is recognized with specificity by antibodies against the human protein Lf. The Lf-65-kDa protein antigenic cross-reactivity may contribute to the formation of autoantibodies and immune complexes as well as to other autoimmune events that are frequent in tuberculosis and leprosy. Our immunocytochemical data also suggest that the cross-reactivity may persist for some time after the death of mycobacteria in infected hosts.

Topics: Animals; Antibody Specificity; Armadillos; Autoimmune Diseases; Bacterial Proteins; Blotting, Western; Cross Reactions; Heat-Shock Proteins; Humans; Immunohistochemistry; Lactoferrin; Leprosy, Lepromatous; Liver; Molecular Weight; Mycobacterium leprae; Mycobacterium tuberculosis; Skin