IgA glycosylation and disease.
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Glomerulonephritis, IGA↗
Biomedical subjects
M Dueymes
Publications and source records attributed to M Dueymes.
Anti CD5 sustains the proliferative response of IgM-activated human CD5+ B cells.
The CD5 molecule is expressed by most T cells but it is present on a minor B cell subset. Whilst several studies have provided information on the physiological role of T cell CD5, the functional role of CD5 on B lymphocytes remains unclear. To address this question, tonsillar CD5+ B cells were sorted by dual-colour fluorescence and FACS. Sorted cells were stimulated with polyclonal anti-IgM antibodies (Ab), and monoclonal (MoAb) F(ab')2 fragments of anti-CD5. Proliferative responses were evaluated by enumeration of Ki-67 positive cells using quantitative flow cytometry. Co-stimulation with anti-CD5 MoAb for 3 days did not affect the anti-IgM and IL2-induced proliferation of CD5+ B cells. This was seen under conditions where the anti-CD5 was soluble, adsorbed to the microwells or cross-linked by anti-mouse antibodies. Fewer CD25+ cells were detected, however, in the presence of anti-CD5. In contrast, the proliferative response of CD5+ B cells prestimulated for 3 days with IL-2 and anti-IgM, was sustained in a further 3-day culture period when anti-CD5 was added. It is concluded that CD5 occupancy might provide an additional signal to activated CD5+ B cells favouring their proliferation and differentiation into autoantibody secreting cells.
Antibodies↗
Role of beta 2-glycoprotein I in the antiphospholipid antibody binding to endothelial cells.
A group of anticardiolipin antibodies (aCL) require beta 2-glycoprotein I (beta 2GPI) to recognize their target, which might be located on endothelial cells (EC) and/or platelets. Following incubation with epithelial cells, 13 of 30 lupus sera retained EC-reactive antibodies of the IgG, IgA and IgM isotypes. Associated aCL and anti-phosphatidylethanolamine antibodies were partly absorbed on eC as well as EC. The former antibodies were more efficiently removed in the presence than in the absence of the latter. The presence of beta 2GPI in the affinity-purified aCL preparations may explain their binding to EC, as this cross-reaction was abrogated by the removal of the cofactor and restored by its re-introduction. Seventy four per cent of EC were faintly stained with polyclonal or monoclonal antibody directed to the cofactor. The beta 2GPI mediated aCL binding to EC membranes could this be influential in the development of thrombosis and/or thrombocytopenia in aCL-positive patients.
Adolescent↗
Role of beta 2-glycoprotein I in the anticardiolipin antibody affinity for phospholipid in autoimmune disease.
The binding capacity to cardiolipin and the functional affinity of affinity-purified anticardiolipin (aCL) IgG of patients with autoimmune disease have been compared with those of individuals with malaria and acquired immunodeficiency syndrome (AIDS). The binding of autoimmune IgG aCL was enhanced gradually by the incorporation of increasing amounts of beta 2-glycoprotein I (beta 2GPI) into the assay, in contrast to that of patients with infectious diseases. In addition, there were significant reductions of functional affinity in autoimmune disease, but not in malaria or in AIDS. These results indicate that beta 2GPI requirement for binding to the target antigen varies inversely with functional affinity in autoimmune disease when beta 2GPI was present, and suggest that IgG aCL are more heterogeneous in this type of disorder than in patients with infectious disease.
Acquired Immunodeficiency Syndrome↗
The relationship of anti-endothelial cell antibodies to anti-phospholipid antibodies in patients with giant cell arteritis and/or polymyalgia rheumatica.
Sera from patients with giant cell arteritis and/or polymyalgia rheumatica were tested for the presence of IgG, IgM and IgA antibody to endothelial cells (AEC), cardiolipin (ACL) and phosphatidylethanolamine (APE) using enzyme-linked immunosorbent assays. There were strong correlations between ACL and APE, but also between AEC and ACL IgM (p < 0.02) and between AEC and APE IgA (p < 0.003). Inhibition of AEC binding was achieved by absorption onto EC, but ACL and APE binding was also significantly reduced. In contrast, the binding of AEC antibody could not be inhibited by incubation with CL. Our data suggest that AEC constitute a heterogeneous population of autoantibodies.
Aged↗
Isotypic distribution of anti-pyruvate dehydrogenase antibodies in patients with primary biliary cirrhosis and their family members.
IgG subclasses of anti-pyruvate dehydrogenase (PDH) antibodies were determined in 72 patients with primary biliary cirrhosis. All isotypes were detected, but IgG3, IgG1, and IgG2 predominated independently or in association. An average of 33.3 +/- 19.1% of the anti-PDH IgG was IgG1 (mean optical density, 0.863 +/- 0.783, vs 0.053 +/- 0.038 in the normal controls), 25.0 +/- 17.8 IgG2 (0.652 +/- 0.656 vs 0.062 +/- 0.030), 39.5 +/- 23.4% IgG3 (1.140 +/- 0.917 vs 0.010 +/- 0.023), and 2.4 +/- 7.4% IgG4 (0.060 +/- 0.182 vs 0.012 +/- 0.007). Anti-PDH IgG were restricted to IgG1 in the family members of patients (0.180 +/- 0.403).
Adolescent↗
Predominance of IgG1 subclass of anti-Ro/SSA, but not anti-La/SSB antibodies in primary Sjögren's syndrome.
We have developed isotype-specific enzyme-linked immunosorbent assays to assess anti-Ro/SSA and anti-La/SSB IgG subclasses in 31 patients with primary Sjögren's syndrome. The anti-Ro/SSA antibody production was largely but not totally restricted to IgG1, whilst the anti-La/SSB subclass distribution varied from one patient to another. IgG2 and IgG3 anti-La/SSB was more frequent in those patients with extraglandular manifestations. In addition, there were more increases in the IgG2 and IgG4 contribution to anti-La/SSB activity in the 16 DR3-positive patients than in the remaining 10.
Adult↗
Relationship of interleukin-4 to isotypic distribution of anti-double-stranded DNA antibodies in systemic lupus erythematosus.
IgG subclasses of anti-double-stranded DNA antibodies were determined in 182 patients with systemic lupus erythematosus. All isotypes were detected, but IgG1 and IgG3 were predominant (62 and 51% of the cases, respectively). An average of 64 +/- 27% was IgG1, 16 +/- 22% IgG2, 16 +/- 19% IgG3 and 4 +/- 10% IgG4. The rank order or frequency was IgG1, IgG3, IgG2 and IgG4 in patients with musculoskeletal involvement; IgG1, IgG2, IgG3 and IgG4 in those with renal complications; IgG3, IgG1, IgG2 and IgG4 in those with cutaneous involvement; and IgG1, IgG3, IgG2 and IgG4 in those with hematological manifestations. Interleukin-4 (IL-4) was detectable in 17 of 36 selected patients, as opposed to 1 of 40 normal controls. The percentage of the total autoantibody contributed by IgG1 was significantly higher (p < 0.03) in these patients than in the remainder with undetectable levels of IL-4.
Adolescent↗
Antibodies to phosphatidylethanolamine in antiphospholipid syndrome and systemic lupus erythematosus: their correlation with anticardiolipin antibodies and beta 2 glycoprotein-I plasma levels.
The sera patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) were tested, by ELISA, for antibodies to phosphatidylethanolamine (aPE), as well as to cardiolipin (aCL) and compared to healthy blood donors (HBD). Both, SLE and APS patients presented a higher titre of IgM-aPE antibodies than normals, while the IgG and IgA aPE reactivity did not differ. APS patients were characterized by higher IgM-aPE antibody titres than SLE patients. In contrast, the predominant isotype of aCL antibodies in APS patients was IgG. The IgM aPE reactivity was correlated with IgM aCL reactivity, while no correlation was observed between the total IgM values and IgM-aPE binding units of sera tested. Since it was shown that beta 2-glycoprotein-I (beta 2-GPI) contributes to a complex antigen by binding to phospholipids and that this antigen is recognized by antiphospholipid antibodies from autoimmune patients, sera beta 2-GPI levels were measured and correlated to aCL and APE activity. Although APS patients had higher beta 2-GPI levels than SLE patients, no correlation was found between the beta 2-GPI levels and IgG/IgM aCL and IgM-aPE reactivities a finding suggesting that in addition to beta 2-GPI, other cofactors for aPE antibodies may exist. These findings indicate that aPE and aCL antibodies co-exist and that the IgM-isotype is predominant in APS. In addition, the IgA and IgG aPE antibodies appear to occur in low titres in these patients, as well as in normals and may exist as natural autoantibodies. We suggest that the high IgM-aPE antibodies may be viewed as a thymus independent process.
Antibodies, Anticardiolipin↗
[Infectious origin of rheumatoid arthritis].
Three preliminary concepts are developed: antigen presentation, "peptidic self" and superantigen. Several infectious contenders for rheumatoid arthritis (RA) are then reviewed: Epstein-Barr virus, mycobacteria, parvovirus, proteus and streptococcus. Finally, the most important hypotheses are discussed: microbe present and still accessible, microbe present but hidden, microbe absent but perpetuated by the immune system. In the latest case, molecular mimicry could possibly be the mechanism operating in RA.
Animals↗
[Autoimmunity and AIDS].
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Acquired Immunodeficiency Syndrome↗
Galactose terminating oligosaccharides of IgG in patients with primary Sjögren's syndrome.
Using a simple but novel ELISA, we have screened 40 serum samples from patients with primary Sjögren's syndrome and 34 normal controls for IgG glycosylation deficiencies, identified by their specific ricin binding. Elevated levels of asialylated IgG were detected in 24 patients. The extent of asialylation was significantly higher in the patients with extraglandular manifestations than in the others. Interestingly, the correlation of asialylated IgG was apparent only with Raynaud's phenomenon and arthritis, and not other extraglandular manifestations. Strong correlations (P less than 0.01) were noted between asialylated IgG and rheumatoid factor or IgA-containing immune complexes.
Adult↗
Anti-neutrophil cytoplasm antibodies in patients with giant cell arteritis and/or polymyalgia rheumatica.
Anti-neutrophil cytoplasm antibodies (ANCA) were detected at low titers by indirect immunofluorescence in 1 out of 13 patients with giant cell arteritis (GCA) alone, 7 out of 30 with polymyalgia rheumatica (PMR) alone and 4 out of 15 with GCA plus PMR (8, 23 and 27%, respectively). Anti-myeloperoxidase antibodies were also demonstrated by an enzyme-linked immunosorbent assay in 4 patients with GCA alone (31%), 13 with PRM alone (42%) and 5 with GCA plus PRM (33%). The C-reactive protein response was significantly higher (p < 0.05) in ANCA-positive than in ANCA-negative patients.
Aged↗
Chronical administration of anti-DNA antibodies by subcutaneous injection of hybridoma clones in BALB/c and NZBxNZW/F1 mice. Experimental model of the pathogenic role of DNA in acute lupus disease.
Several sets of data suggest that specific classes of anti-DNA antibodies could be implicated in the genesis of glomerular lesions in SLE. The goal of this work is to investigate if this pathogenic role could be related to the antibodies' genetic origin--from BALB/c or NZBxNZW/F1 mice--or to their physiological origin--induced either by DNA or by polyclonal B cell activation in normal mice. For this purpose, anti-DNA antibody hybridoma clones produced from different origins were subcutaneously injected in BALB/c or NZBxNZW/F1 female mice, followed by studies of immunological parameters and kidney lesions. Results concur that the induced anti-DNA antibodies can play a role in fatal disease development, related to clonal specificity but not to the way of stimulation which was either polyclonal B cell activation or DNA immunization. Also, they emphasize the possible very lethal role of serum circulating DNA.
Acute Disease↗
Modulation of polyclonal activation of lymphocytes by cyclophosphazenic compounds bearing ethylene-imino groups and vectorized by polyamines.
Cyclophosphazenic compounds bearing ethylene-imino groups are cytocydal chemicals which can modulate polyclonal activation of lymphocytes (PAL) and prevent the development of murine lupus. The effects on PAL of the different parts of these chemicals and of vectorization by polyamines have been investigated by treating lipopolysaccharide injected C57Bl/6 mice with various cyclophosphazenic compounds and thiotepa. The immune effects of the cyclophosphazenic substances have been found to be mediated by ethylene-imino groups and to be modulated by polyamine vectorization. These compounds might represent a new class of drugs for treatment of immune mediated diseases of the lupus type.
Adjuvants, Immunologic↗
Treatment of end stage MRL-1pr/lpr mouse lupus disease by a cyclophosphazene derived drug and by cyclosporin A.
MRL-lpr/lpr mice develop T cell lymphadenopathy, polyclonal activation of B lymphocytes, autoantibodies and lupus nephritis. B and T cell populations, the dysfunctions of which play a role in the pathophysiology of the mouse disease, represent potential targets for lupus treatment. MRL-lpr/lpr mice are treated from the age of 19 weeks, i.e. after the onset of renal disease and lymphoproliferation, with Cyclosporin A which acts at the T cell level, or with DIAM4 which can down modulate polyclonal activation of B lymphocytes. DIAM4 induces the disappearance of the lymphoproliferation, the increase in C3 levels and the decrease in anti-DNA antibody, immunoglobulin and urea levels, and proteinuria. Cyclosporin A reduces lymph node hyperplasia, but has no effect on other parameters of the disease.
Age Factors↗
Mesangial staining with cytomegalovirus antibodies in IgA nephropathy.
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Antibodies, Viral↗
Beta blockers may induce in C57BL/6 mice a polyclonal activation of lymphocytes which is not mediated by beta adrenergic receptors.
The in vivo immune effects of nine beta (beta)-blockers are studied in C5B1/6 mice after 7 days of treatment. Humoral and cellular studies indicate that several beta-blocking agents, particularly pindolol and acebutolol, may induce a polyclonal activation of lymphocytes. It may involve all the classes and subclasses of immunoglobulins with a preferential effect on IgA and IgG2a. Further investigations, conducted using the laevorotatory and dextrorotatory forms of pindolol indicate that this immune effect is not mediated by specific beta-adrenergic receptors.
Acebutolol↗