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Biomedical subjects

M Reichlin

Publications and source records attributed to M Reichlin.

At least 19 recordsLinked to original sources
PubMed1992

Antibodies to carbonic anhydrase in systemic lupus erythematosus and other rheumatic diseases.

OBJECTIVE: Autoantibodies to CA were demonstrated in the sera of patients with systemic lupus erythematosus (SLE) and some other rheumatic diseases. This study was undertaken to define the isoform and species specificity of these reactions, as well as to develop a method for detecting immune complexes. METHODS: Antibodies to CA were sought by enzyme-linked immunosorbent assay (ELISA) and by Western immunoblotting. RESULTS: An increased prevalence of CA autoantibodies was detected, by both methods, in patients with SLE, scleroderma, and polymyositis, compared with controls. In SLE patients, CA autoantibodies occurred preferentially in those with anti-U1 RNP or anti-U1 RNP and Ro/SS-A. Some sera reacted with only the CA I or CA II isoform, while approximately 50% of sera that were CA positive reacted with both isoforms. The autoantibodies reacted preferentially with the human enzymes, rather than the bovine CA, both on Western blot and by ELISA: Selected IgG F(ab')2 fragments from anti-CA-containing sera specifically inhibited the enzyme activity of CA, and the CA inhibitor acetazolamide partially inhibited the binding of anti-CA to CA. Thus, at least a part of autoanti-CA is directed toward the active site of CA. Finally, CA molecules were detected as immune complexes in sera from selected anti-CA-positive patients. CONCLUSION: Autoantibodies to CA represent a previously unrecognized autoantibody to an abundant intracellular protein of the human erythrocyte.

Acetazolamide↗
PubMed1992

Serologic studies of monozygotic twins with systemic lupus erythematosus.

OBJECTIVE: The goal of these studies was to assess the role of genetic factors and disease expression in the pattern and titer of autoantibodies to several RNA protein antigens in patients with systemic lupus erythematosus (SLE) by studying identical twins concordant and discordant for disease expression. METHODS: Autoantibodies to Ro/SS-A, La/SS-B, U1 RNP, and Sm were measured by quantitative enzyme-linked immunosorbent assay using affinity-purified antigens. RESULTS: Detailed serologic studies were performed in 7 pairs of identical twins, 3 of whom were concordant and 4 of whom were discordant for disease expression. Autoantibody titers were higher in affected than in unaffected twins from discordant pairs, but in 3 of 4 pairs, the profile of anti-RNA proteins (e.g., Ro/SS-A, La/SS-B, U1 RNP, and Sm) was virtually identical. In the SLE pairs concordant for disease expression, the autoantibody titers were very similar, as were the anti-RNA protein profiles. When the identical twins were matched by sex, race, and age to pairs of nontwin SLE patients, the 6 white twins shared an average of 2.5 (+/- 1.05 SD) anti-RNA proteins, while the control SLE pairs shared only 0.33 (+/- 0.82), P less than 0.01 (t = 4.0, P less than 0.01). In addition, in the white SLE twins, all had elevated levels of anti-U1 RNP while in white nontwin SLE patients, the frequency of anti-U1 RNP was 30%. CONCLUSION: These data point to a dominant role for genetic factors in the determination of specific autoantibody profiles.

Antigen-Antibody Reactions↗
PubMed1992

Autoantibodies to the ribosomal P proteins react with a plasma membrane-related target on human cells.

Autoantibodies to ribosomal P-proteins are present in 12-16% of patients with systemic lupus erythematosus and are associated with neuropsychiatric disease. As the ribosomal P proteins are located in the cytoplasm, the pathogenic effects of their cognate autoantibodies are unclear. In this study affinity-purified anti-P autoantibodies were used to explore the cell surface of several types of human and animal cells. Immunofluorescence as well as EM immunogold analysis demonstrated, on the surface of human hepatoma cells, the presence of an epitope that is antigenically related to the immunodominant carboxy terminus of P-proteins. The presence of this epitope was also demonstrated on the surface of human neuroblastoma cells and, to a lesser extent, on human fibroblasts. Furthermore, the Western blot technique revealed in purified human and animal plasma membranes a 38-kD protein that is closely related or identical with ribosomal P0 protein. The availability of reactive P peptide on the surface of cells makes possible the direct effect of autoantibodies on the function and viability of cells that express this antigenic target. This delineates one of the possible impacts of anti-P antibodies in disease expression.

Amino Acid Sequence↗
PubMed1992

Two sisters producing anti-U1RNP exhibit serological concordance and clinical discordance.

Two sisters had autoimmune responses to the U1RNP particle that were quantitatively similar and/or identical in molecular characteristics. No other autoantibodies were demonstrable. Both sisters immunoprecipitated only U1RNA, had a reaction of identity in gel diffusion, bound the 68-kDa band in HeLa cell extract in Western blot, and reacted almost equally to a rabbit anti-idiotypic reagent made against either sister's isolated anti-U1RNP Fab fragments. They both carried a DR4 allele, which has been associated with anti-U1RNP production in several studies. While the sisters both had Raynaud's phenomenon, their clinical pictures were otherwise dissimilar. One had a seizure disorder (Ju); the other had polymyositis and features of scleroderma (Je). In sister Ju, Raynaud's phenomenon was manifest for the first time in association with the appearance of precipitating anti-U1RNP.

Adult↗
PubMed1992

Autoantibodies to the Ro/SSA autoantigen are conformation dependent. II: Antibodies to the denatured form of 52 kD Ro/SSA are a cross reacting subset of antibodies to the native 60 kD Ro/SSA molecule.

The immune response to the Ro/SSA particles is conformation dependent. In sera with only anti-Ro/SSA precipitins, the autoantibodies to the 60 kD Ro/SSA are largely to the native 60 kD Ro/SSA while autoantibodies to the 52 kD Ro/SSA particle when present are exclusively to the denatured 52 kD Ro/SSA particle. Antibodies eluted from a recombinant 52 kD Ro/SSA fusion protein reacted in a sandwich ELISA which only measures antibody to native 60 kD Ro/SSA antigens and this reaction is largely inhibited by native homogeneous 60 kD Ro/SSA. In addition, antibody binding to the 52 kD Ro/SSA antigen in Western blot is also strongly inhibited by native 60 kD Ro/SSA. These experiment strongly suggest that reactivity of denatured 52 kD Ro/SSA antigen represents a cross reaction with autoantibodies directed to the native 60 kD Ro/SSA antigen. As a corollary of these experiments, data are presented that suggest the hY-RNAs are not associated with the 52 kD Ro/SSA protein but only with the 60 kD Ro/SSA protein. These data are consistent with the hypothesis that the autoanti-Ro/SSA response is driven by native 60 kD Ro/SSA and the immune response to denatured 52 kD Ro/SSA is largely a cross-reactive subset of the immune response to native 60 kD Ro/SSA.

Antibody Specificity↗
PubMed1992

Autoantibodies to the Ro/SSA antigen are conformation dependent. I: Anti-60 kD antibodies are mainly directed to the native protein; anti-52 kD antibodies are mainly directed to the denatured protein.

Recent studies have shown that Ro/SSA autoantigen is heterogeneous and the autoanti-Ro/SSA response is correspondingly heterogeneous. There are two isoform families; the 60 kD forms and the 52 kD forms. We studied the antigenic difference between the native and denatured Ro/SSA isoforms and found that the autoanti-Ro/SSA response to the native 60 kD antigen is quite homogeneous. All anti-Ro/SSA sera recognize the native kD antigen regardless of the reactivities to the 60 kD band on the Western blot. Surprisingly, no anti-Ro/SSA sera without anti-La/SSB reacts with the native 52 kD Ro/SSA, although sera with both precipitating anti-Ro/SSA and anti-La/SSB can immunoprecipitate the native 52 kD antigen. Anti-Ro/SSA sera exist which react exclusively with the native 60 kD Ro/SSA protein (10/43, 23%) while no anti-Ro/SSA sera have been found which react exclusively with the denatured 52 kD Ro/SSA antigen. In sera with anti-Ro/SSA precipitins alone, only antibody to the denatured 52 kD Ro/SSA molecule is found! In sera with anti-Ro/SSA and anti-U1 RNP precipitins, no antibody to either native or denatured 52 kD Ro/SSA is found, while in sera with both anti-Ro/SSA and anti-La/SSB precipitins, antibodies to both the native and denatured forms of 52 kD Ro/SSA are present. These data suggest that the anti-Ro/SSA response to the 60 kD molecule is driven by the native 60 kD Ro/SSA molecule while the molecular identification of the antigen drive in the anti-52 kD Ro/SSA response is unknown.

Antibodies, Antinuclear↗
PubMed1992

Anti-Ro in Sjögren's syndrome and systemic lupus erythematosus.

Anti-Ro autoantibodies are frequently found in the sera of patients with Sjögren's syndrome, systemic lupus erythematosus, and subacute cutaneous lupus erythematosus as well as in the sera of mothers of infants with the neonatal lupus syndrome. Close associations have been found between anti-Ro and a number of clinical manifestations, particularly including hematologic cytopenias, heart block, and photosensitive skin rashes. Serologic and genetic associations have been found between anti-Ro and anti-La, rheumatoid factor, hypergammaglobulinemia, the histocompatibility alleles DQ1 and DQ2, and alleles of the T-cell receptor beta chain gene. The origin of anti-Ro and other autoantigens is thought to relate to the etiology of Sjögren's syndrome and systemic lupus erythematosus and remains the most fundamental unanswered question preventing a comprehensive understanding of these diseases.

Antibodies, Antinuclear↗
PubMed1991

Twenty percent of biopsy specimens from sun-exposed skin of normal young adults demonstrate positive immunofluorescence.

Fifty normal healthy adults, aged 18 to 41 years, without a history of systemic diseases, dermatoses, or photosensitivity and who were not receiving medication were studied. Paired 3-mm punch biopsy specimens were obtained from the sun-exposed and the non-sun-exposed skin. The data from the study revealed a bright continuous band of immunofluorescence (IF) along the dermoepidermal junction in 10 (20%) of 50 sun-exposed skin biopsy specimens, as compared with none from non-sun-exposed skin biopsy specimens with the use of polyvalent antisera. Fractionated monospecific immunoglobulin demonstrated a bright continuous band of IF composed of IgG alone in one patient, IgA alone in two patients, IgG and IgA in combination in two patients, and the combination of IgG, IgM, and IgA in five patients. There was a statistically significant increase in positive IF in men (seven of 15) vs women (three of 35). This information suggests that in the examination of a patient suspected of having lesions of cutaneous lupus erythematosus, positive IF from sun-exposed skin is nonspecific and adds little information to the clinical and histopathologic findings.

Adolescent↗
PubMed1991

Ro/SS-A antigen in human platelets. Different distributions of the isoforms of Ro/SS-A protein and the Ro/SS-A-binding RNA.

Ro/SS-A antigen is present in human platelets at a concentration that is approximately one-twentieth to one-thirtieth its concentration in lymphocytes, but the distribution of the Ro/SS-A isoforms is different from that in lymphocytes or red blood cells. The Ro/SS-A in platelets is largely the 52-kd form. Moreover, the 52-kd isoform in platelets is antigenically different from that in lymphocytes. In addition to the varied isoform distribution, a different distribution of the Ro/SS-A-binding RNA (hY RNA) is seen in platelets. While there are 4 hY RNA (hY1, hY3, hY4, and hY5) in lymphocytes and other nucleated cells, we have found that platelets contain only 2 hY RNA: hY3 and hY4. This hY RNA distribution is also different from that in red blood cells, which contain only hY1 and hY4. The different distributions of the Ro/SS-A components in lymphocytes, red blood cells, and platelets suggest different functional roles for the various protein and RNA components, as well as the possibility of different tissue-specific events related to the Ro/SS-A-autoanti-Ro/SS-A system.

Autoantigens↗
PubMed1991

Cerebral vasculopathy associated with collateralization resembling moya moya phenomenon and with anti-Ro/SS-A and anti-La/SS-B antibodies.

We describe a 48-year-old, previously healthy, anti-Ro/SS-A and anti-La/SS-B antibody positive black woman with negative risk factors for atherosclerosis, who developed mental status and personality changes over a 6-12-month period, and progressive cortical blindness over a 2-week period. Angiographic and computed axial tomographic studies of the brain demonstrated multiple large areas of infarction correlating with stenosis and occlusions of the internal carotid and posterior cerebral arteries. Moya moya-like findings were prominent radiographically. Results of angiographic, computed tomographic, and magnetic resonance imaging studies were interpreted as being compatible with large, medium, and small vessel disease, most likely a vasculitis.

Angiography↗
PubMed1991

Autoantibodies to the URNP particles: relationship to clinical diagnosis and nephritis.

Precipitating autoantibodies to the URNP particles were used to select 80 patients, and were further characterized by immunoblotting and quantitative ELISA. These immunochemical results have been related to clinical diagnosis, the frequency of nephritis, and Raynaud's phenomenon. Autoantibodies to the 70-kD polypeptide of the U1RNP particle were present in 16 out of 19 patients with mixed connective tissue disease (MCTD) and in 27 out of 61 patients with systemic lupus erythematosus (SLE). The ratio of anti-U1RNP/Sm by ELISA and the frequency of antibody to 70-kD protein were directly related to the frequency of Raynaud's phenomenon and inversely related to the frequency of nephritis.

Autoantibodies↗