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M Reichlin

Publications and source records attributed to M Reichlin.

At least 73 records · Page 4Linked to original sources
PubMed1995

Anti-ribosomal P antibodies in systemic lupus erythematosus: a case-control study correlating hepatic and renal disease.

We report a case-control study of the occurrence of liver and kidney disease in 20 systemic lupus erythematosus (SLE) patients with anti-ribosomal P antibodies and 20 age-, sex-, and race-matched (control group) SLE patients without anti-P antibodies. In the group with anti-P antibodies, 7 patients were found to have had liver disease, compared with only 1 in the control group (P = 0.03), and 14 anti-P (+) patients have had kidney disease, compared with 4 in the control group (P = 0.01). A major serological difference between the groups was an increased prevalence of anti-dsDNA in the anti-P positive group (12/20) vs the control group (4/20), P = 0.02. These statistically significant differences suggest that antibodies to ribosomal P identify a subset of SLE patients at higher risk for liver and kidney involvement, in addition to the previously recognized risk for neuropsychiatric disease.

Adolescent↗
PubMed1995

Lupus hepatitis: an under-recognized disease feature associated with autoantibodies to ribosomal P.

PURPOSE: To determine the frequency and clinical manifestations of systemic lupus erythematosus (SLE)-related liver disease and to establish whether this disease feature correlates with circulating autoantibodies to ribosomal P proteins. PATIENTS AND METHODS: A retrospective chart review of a large lupus cohort searching for laboratory and clinical manifestations of liver disease. A case-control study with testing of stored serum for antiribosomal P antibodies using immunoblotting, an enzyme-linked immunosorbent assay, and immunodiffusion in cases of lupus with liver involvement, and in randomly selected and ethnically-matched controls with lupus but without liver involvement. RESULTS: Of 131 patients with SLE, 4 (3%) had liver involvement that could only be ascribed to the disease itself, and 2 additional cases from elsewhere were also studied. The clinical picture of the liver involvement resembled chronic active hepatitis, but there was no serological evidence of hepatitis B or C infections. Only 1 patient had low-titer antismooth muscle antibodies, and none had antimitochondrial antibodies. Antiribosomal P antibodies were present in all 6 patients with lupus hepatitis, compared to only 2 (10%) of 20 of controls with lupus but no liver disease (P = 0.0001, odds ratio 96). CONCLUSIONS: Lupus hepatitis appears to be an infrequent but distinct manifestation of SLE which correlates strongly with the presence of antiribosomal P antibodies. Its course and prognosis are variable, ranging from chronic biochemical abnormalities of liver function to acute clinical hepatitis to hepatic failure.

Adolescent↗
PubMed1995

Anti-p57: a novel association with neonatal lupus.

IgG antibodies to a 57-kD protein (p57) present in various human and bovine extracts were detected by immunoblotting in the serum of the mother of a baby with congenital heart block, but not in the corresponding cord blood, suggesting specific antibody consumption in the baby. Since this indicates a possible functional role for these antibodies, the antigen target was characterized and the association of the antibodies to heart block was further studied. A human K562 lambda gt11 cDNA library was screened and two clones were identified whose products reacted with the prototype serum. Antibody affinity-purified by use of the cloned gene products reacted on immunoblot with the 57-kD band. Partial sequences of both inserts were identical, but differed from DNA encoding the Ro(SSA) and La(SSB) antigens. Antibodies to the p57 were detected in 10% of systemic lupus erythematosus (SLE) sera, almost exclusively in association with anti-Ro(SSA). Furthermore, they were present in 38% (8/21) mothers of babies with neonatal lupus expressing either cardiac or cutaneous manifestations. Antibodies to this 57-kD protein may be an additional risk factor for neonatal lupus in anti-Ro-positive women. Moreover, disappearance of antibody from cord blood suggests that they may have a role in disease manifestations.

Autoantibodies↗
PubMed1994

Is there an association between injectable collagen and polymyositis/dermatomyositis?

OBJECTIVE: Recent case reports have raised the possibility that use of injectable bovine collagen may be associated with polymyositis/dermatomyositis (PM/DM). Because the number of collagen users is high, PM/DM would be expected to occur in some for reasons unrelated to the collagen use. A central issue is whether the number of observed cases exceeds the number expected on the basis of background rates alone. The present study was undertaken to investigate this. METHODS: The number of observed cases was determined by review of the medical records of collagen users who had reported illnesses consistent with PM/DM: Because of the uncertainty about diagnosis of PM/DM, population incidence rates, number of patients treated with collagen, and duration of followup after treatment, we examined a range of estimates of each of these factors that would affect the expected number of cases. RESULTS: From reports among collagen users, 7 probable or definite cases of PM/DM were confirmed. In contrast, 13 cases would be expected based on the best estimates of relevant factors. Under the most conservative estimates for factors that influence the number of expected cases, 12 cases would be expected, while worst-case assumptions would yield an expected 130 cases. CONCLUSION: The consistent finding of fewer-than-expected PM/DM cases among collagen users suggests that collagen use is not associated with the development of PM/DM:

Adolescent↗
PubMed1994

Concentration of autoantibodies to native 60-kd Ro/SS-A and denatured 52-kd Ro/SS-A in eluates from the heart of a child who died with congenital complete heart block.

OBJECTIVE: To determine the serologic specificity of acid eluates from tissues of a child who died with congenital complete heart block (CCHB). METHODS: Tissues were extracted, acid eluted, and the IgG and antibody titers determined on the eluates by enzyme-linked immunosorbent assay. RESULTS: Antibodies to native 60-kd and denatured 52-kd Ro/SS-A were found to be enriched only in the heart eluate, and not in the eluates from brain, kidney, and skin. CONCLUSION: These findings indicate a major role for anti-native 60-kd Ro/SS-A in the immunopathogenesis of CCHB.

Adult↗
PubMed1994

Autoantibodies to decondensed sperm nuclear deoxyribonucleic acid in patients with antisperm antibodies and systemic lupus erythematosus detected by immunofluorescence flow cytometry.

OBJECTIVE: To evaluate a flow cytometric method to detect and quantitate serum anti-DNA antibodies using unfixed, swollen and decondensed human sperm nuclei and to examine the relationship between antibodies against sperm surface antigens to the presence of antibodies against nuclear antigens. DESIGN: Serum IgG and IgG subclass antibodies to decondensed sperm nuclei were detected by indirect immunofluorescence (IIF) flow cytometry. Sera were screened by IIF for anti-double-stranded DNA antibodies using the protozoan Crithidia luciliae as the substrate and for antinuclear antibodies using human epithelial (HEp 2) cells, respectively. All sera were assessed for antibodies against the sperm plasma membrane by an indirect immunobead test. SETTING: Infertility laboratory at the University of Oklahoma Health Sciences Center and rheumatology laboratory at the Oklahoma Medical Research Foundation. PATIENTS: Sera from 33 antisperm antibody-positive patients (5 subgroups), 33 patients with systemic lupus erythematosus (SLE; 6 subgroups), and 20 normal controls were selected. RESULTS: IgG antibodies against decondensed sperm nuclear DNA were detected in 11 (33.3%) of 33 antisperm antibody-positive patients versus 14 (42.4%) of 33 patients with SLE. Anti-DNA antibodies were most prevalent in vasectomized men and in antisperm antibody positive women with SLE. In the sera from patients with SLE, the presence of the anti-nuclear ribonucleoprotein antibody was associated with the presence of sperm head-directed antisperm antibodies. Anti-double-stranded DNA antibodies were found in 6 (18.1%) of 33 sera from patients with antisperm antibody and 17 (51.5%) of 33 sera from patients with SLE. Antinuclear antibodies were found in only 9 (27.2%) of 33 sera from patients with antisperm antibody and 30 (90.9%) of 33 sera from patients with SLE. All 20 of the control sera gave negative results in the three tests. Serum IgG reactivity to sperm nuclei was predominantly of the IgG1 and IgG3 subclasses. CONCLUSION: Anti-DNA is frequently found in either patients with antisperm antibodies or patients with SLE. Our results indicated that decondensed sperm nuclei can provide a specific substrate for screening serum anti-DNA antibodies.

Antibodies↗
PubMed1994

Observations on the epistemological status of bioethics.

Different definitions of bioethics in American and Italian literature are reported. It is argued that they refer to three different conceptions of the epistemological status of bioethics: the first conceives of it as an application of moral principles to biomedical problems, the second as a methodology for the working out of clinical judgement, the third as a broader and interdisciplinary public inquiry. It is suggested that each approach grasps a part of the truth, for each singles out one level of the bioethical work. Bioethics is in fact a complex, three-level form of knowledge. The misunderstanding of this complexity has led to some confusion and to conflicts of attribution among those who are concerned with it.

Beneficence↗
PubMed1994

Autoantibodies of neonatal lupus erythematosus.

The most common manifestations of neonatal lupus erythematosus (NLE) are cutaneous lupus and congenital heart block. Autoantibodies to Ro/SSA occur in almost all cases of NLE. The autoantibody response to Ro/SSA is complex, and antibodies may be detected to 60-kD Ro/SSA, 52-kD Ro/SSA, La/SSB, and U1 ribonuclear protein in anti-Ro/SSA-positive sera. Which of these anti-Ro/SSA-related autoantibody specificities are important in the clinical expression of NLE is not conclusively established. We examined the autoantibody specificities in 20 maternal NLE sera to determine whether autoantibody specificities correlate with the clinical findings and to evaluate the relative importance of autoantibodies to the different Ro/SSA-associated proteins. Autoantibodies were examined using immunodiffusion, immunoblotting, and enzyme-linked immunosorbent assay. Eleven babies had NLE skin disease, 11 had heart block, and two had both skin disease and heart block. All 20 maternal sera had antibodies to 60-kD Ro/SSA. Eighteen of the 20 had antibodies to 52-kD Ro/SSA, nine had antibodies to La/SSB, and one had antibodies to U1 ribonuclear protein. The prevalence of anti-La/SSB was the same in the skin-disease and heart-block subsets of NLE. Titers of anti-60-kD Ro/SSA were significantly (p < 0.02) lower in NLE skin disease maternal sera than in the NLE heart-block maternal sera. These results point out the importance of 60-kD Ro/SSA as a potential target in NLE. We speculate that the lower titers of anti-60-kD Ro/SSA in the sera from mothers of babies with skin disease may be due to substantial deposition of antibodies in the mothers' and babies' skin, leading to lower circulating titers, or may reflect a lower threshold for development of skin disease than for heart block.

Antibodies, Antinuclear↗
PubMed1994

Lupus autoantibodies to native DNA cross-react with the A and D SnRNP polypeptides.

Antibodies to native DNA (nDNA) in sera from patients with systemic lupus erythematosus have been found to frequently correlate with antibodies to the A and D SnRNP proteins measured in Western blot assays. 40 of 54 SLE (74.1%) sera with anti-nDNA bound to A and D proteins, while 9 of 113 sera (8%) without anti-nDNA bound the A and D proteins, P < 10(-8) by Fisher's exact test. Antibodies to nDNA correlated closely with anti-A and anti-D in seven of eight patients followed sequentially, r = 0.7865. Nine human polyclonal anti-nDNA populations were isolated from DNA cellulose columns. Seven reacted equally with A and D, and two reacted predominantly with D. Two of three murine monoclonal anti-DNA antibodies isolated from NZB/NZW F1 hybrid mice bound A and D equally in Western blot with a titer > 1/40,000. These reactions were directed to the unfolded A and D proteins measurable in Western blot since these monoclonals (and several of the human anti-nDNA populations) failed to react with native U1RNP in ELISA or in RNA immunoprecipitation experiments. These newly recognized cross reactions of anti-nDNA may amplify the immune response to DNA and be part of the original immunogenic drive.

Animals↗
PubMed1994

Anti-Ro(SS-A) autoantibodies in central nervous system disease associated with Sjögren's syndrome (CNS-SS): clinical, neuroimaging, and angiographic correlates.

OBJECTIVE: To examine in Sjögren's syndrome (SS) the interrelationship between the presence of the anti-Ro(SS-A) antibody response and (1) concomitant presence and type (ie, focal or nonfocal) of CNS disease (CNS-SS), (2) cross-sectional brain MRI or CT, and (3) abnormal cerebral angiography. METHODS: Neurologic, neuroimaging, and angiographic features of CNS-SS patients were correlated with the presence of precipitating anti-Ro(SS-A) autoantibodies detected by gel double-immunodiffusion or quantitative ELISA, which detects antibodies directed against the 60-kd peptide. Statistical analyses were performed using Fisher's exact test (two-tailed) with Haldane's adjustment and odds ratio with Cornfield 95% confidence intervals. RESULTS: Precipitating antibodies against the Ro(SS-A) antigen, determined by gel double-immunodiffusion, were present in an increased frequency in CNS-SS patients with (1) documented clinical CNS disease, (2) focal clinical CNS manifestations and serious complications, (3) large regions of increased signal intensity, consistent with ischemia/infarcts on brain MRI scans or regions of decreased attenuation consistent with infarcts on CT, and (4) abnormal cerebral angiograms consistent with small-vessel angiitis. Finally, the anti-Ro(SS-A) antibody response in CNS was directed against the 60-kd peptide specificity, determined by ELISA. CONCLUSIONS: Clinical, neuroimaging (cerebral CT), and angiographic observation suggest that a subset of anti-Ro(SS-A) antibody-positive, in contrast with -negative, CNS-SS patients have more serious and extensive CNS disease, some with frank cerebral angiopathy. Anti-Ro(SS-A) antibodies are postulated to play a role in mediating or potentiating vascular injury in CNS-SS.

Autoantibodies↗
PubMed1994

The autoantibody response to Ro/SSA in cutaneous lupus erythematosus.

BACKGROUND AND DESIGN: Seventeen patients with subacute cutaneous lupus erythematosus (SCLE) were compared with 15 patients with discoid lupus erythematosus (DLE) to evaluate the relationship of 60- and 52-kd Ro/SSA autoantibodies to the clinical diagnosis and to evaluate assays for anti-Ro/SSA. RESULTS: All serum samples from patients with SCLE had precipitating anti-Ro/SSA antibodies in immunodiffusion, and all had high titer anti-60-kd Ro/SSA in enzyme-linked immunosorbent assay. Immunoblotting was inadequately sensitive for detecting anti-60-kd Ro/SSA. Fifteen patients with SCLE had anti-52-kd Ro/SSA (11 high titer, four low titer). Only one of the 15 patients with DLE had precipitating, high-titer anti-Ro/SSA. Nine other patients with DLE had low-titer anti-60-kd Ro/SSA, and four had low-titer anti-52-kd Ro-SSA. Low-titer anti-Ro/SSA did not confer an increased risk for photosensitivity in the DLE group. CONCLUSIONS: High-titer, precipitating antibodies to Ro/SSA are typical of SCLE and unusual in DLE. Low-titer, nonprecipitating antibodies to Ro/SSA are common in DLE and could be an indication of pathogenic factors shared with SCLE. However, low titers of anti-Ro/SSA do not confer a significant risk for SCLE skin lesions. For the purpose of clinical evaluation of skin disease, immunodiffusion assays for anti-Ro/SSA are cost-effective and informative.

Autoantigens↗
PubMed1994

Systemic lupus erythematosus. Antibodies to ribonuclear proteins.

This review has emphasized that utility of measuring the autoimmune responses to several RNP antigens in the diagnosis of SLE, as well as their use in delineating clinical subsets. The future of this area lies in the definition of the pathogenetic mechanisms that link these autoimmune responses to clinical expression of disease.

Antibodies, Antinuclear↗
PubMed1993

[5 years of dosage intensification and autologous bone marrow or peripheral stem cell transfusion in malignant lymphoma with a high risk of recurrence].

Clinical results of the treatment of malignant lymphomas with a high risk of relapse by dose intensification and autologous bone marrow transplantation are reported. Since 1988, 68 patients with a median age of 34 years (range 16 to 56 years) received dose intensification, including 25 non-Hodgkin's lymphomas in first remission (12 lymphoblastic or Burkitt's lymphomas and 13 large cell lymphomas with risk factors), 20 aggressive non-Hodgkin's lymphomas in chemosensitive relapse, and 23 Hodgkin's lymphomas in chemosensitive relapse. The calculated 3-year overall survival and relapse-free survival was 72% (CI: 57-82%) and 61% (CI: 47-73%) respectively. Treatment related deaths were seen in 4.4%. The median duration of hospitalization was 30 days (range 19-51 days). The relapse-free 3-year survival for the separate treatment groups was 80% for lymphoblastic and Burkitt's lymphomas in first remission, 77% for large cell lymphomas with clinical risk factors in first remission, 39% for aggressive non-Hodgkin's lymphomas in chemosensitive relapse, and 59% for Hodgkin's lymphomas in chemosensitive relapse. These excellent results were obtained with acceptable toxicity and justify the use of dose intensification for a group of young patients with high risk lymphomas.

Adolescent↗
PubMed1993

Concomitant development of chronic active hepatitis and antibodies to ribosomal P proteins in a patient with systemic lupus erythematosus.

We describe a systemic lupus erythematosus (SLE) patient who for several years had typical SLE features and positive antinuclear antibodies (ANA), including anti-native DNA. Over the course of a year, 4 years after the SLE was diagnosed, the ANA disappeared and antibodies to cytoplasmic component ribosomal P protein (anti-P) appeared. Associated with the appearance of anti-P antibodies was the development of biochemical evidence of liver disease, later shown histologically to be chronic active hepatitis. The temporal relationship between the occurrence of anti-P antibodies and the development of liver disease raises the possibility of a role for anti-P antibodies in liver disease.

Adult↗
PubMed1993

A distinctive autoantibody profile in black female patients with lupus nephritis.

OBJECTIVE: Lupus nephritis has often been associated with anti-DNA, but, based on the findings in eluate studies, it appears that other antigen-antibody reactions, such as those involving anti-Ro/SS-A, anti-nuclear RNP (anti-nRNP), and/or anti-Sm, may also contribute to the pathogenesis of nephritis. In the present investigation, we identified and further studied a distinctive precipitin profile present in black women with nephritis. METHODS: Longitudinal clinical and serologic studies of a cohort of university-based systemic lupus erythematosus (SLE) patients (n = 120) were carried out over an 8-year period. RESULTS: A subset of 20 black female patients was identified, of whom 8 had lupus nephritis (group I) and 12 did not (group II). Group I was characterized by a distinct precipitin profile consisting of anti-Ro/SS-A, anti-SM, and anti-nRNP, but no anti-La/SS-B. SLE disease duration at presentation was significantly shorter in group I than in group II (mean 1.94 years versus 5.21 years; P = 0.02). The distinctive precipitin profile of anti-Ro/SS-A, anti-Sm, and anti-nRNP occurred exclusively in group I patients (6 of 8, versus 0 of 12 in group II; P < 0.001). In white lupus nephritis patients, this precipitin profile was not seen. CONCLUSION: While the mechanism responsible for the relationship of this distinctive serologic profile to the development of nephritis in black female lupus patients remains to be determined, its presence may be used as a marker for severe and progressive renal disease.

Autoantibodies↗