Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
8825713 Follow-up study of clinical and immunological findings in patients presenting with acute p 1996 Jan This study was undertaken to examine the natural history of parvovirus B19 infection in persons without a known immune defect in terms of both clinical symptoms and immune responsiveness to the virus. Fifty-three patients with acute B19 infection (positive for serum anti-B19 IgM) were studied; symptoms at acute infection were rash and arthralgia (n = 26), rash (n = 7), arthralgia (n = 16), aplastic crisis (n = 3), and intrauterine fetal death (n = 1). Patients were followed for 26-85 months (mean 57 months) and reassessed for persistent symptoms, anti-B19 antibodies, and antibodies to the unique region of B19 VP1. There were 23 cases of arthralgia persisting for longer than 1 year after acute infection. One of these patients, a 48-year-old woman at follow-up, had had persistent arthralgia for 4 years following acute B19 infection, had rheumatoid factor at a titre of 1920 IU/ml detected at follow-up, and had been independently diagnosed as having rheumatoid arthritis at the time of follow-up. All 53 patients were positive for serum anti-B19 IgG compared to 45 of 53 age- and sex-matched control patients, a significant difference (two-tailed P value = 0.008). All test patients at follow-up and control patients were negative for serum anti-B19 IgM and antibodies to the unique region of B19 VP1. Serum from acute infection from 33 of 53 test patients was tested for antibodies to the unique region of VP1, and 16 of these were positive. The presence of this antibody did not correlate with subsequent duration of symptoms but did correlate with a short interval between symptom onset and blood sampling. The unique region of B19 VP1 is known to be crucial for a successful humoral response to the virus, and it seems that the antigenic role played by this region is important only during the acute phase of B19 infection.
7898050 Localization of matrix metalloproteinase 9 (92-kilodalton gelatinase/type IV collagenase = 1995 Mar BACKGROUND: Matrix metalloproteinase 9 (MMP-9, 92-kD gelatinase/type IV collagenase = gelatinase B) is a member of the MMP gene family and implicated in tissue destruction in the various pathophysiologic conditions. Our previous study showed that MMP-9 purified from human fibrosarcoma cells can cleave the cross-link-containing NH(2)-terminal telopeptides of the alpha 2 chain of type I collagen and collagen types III, IV, and V as well as gelatins. EXPERIMENTAL DESIGN: To investigate the role of MMP-9 in bone resorption we have examined its localization in the human bone tissues by immunohistochemistry and in situ hybridization. The enzymic properties were also biochemically studied. RESULTS: Immunohistochemistry using monoclonal antibodies against MMP-1 (interstitial collagenase), MMP-2 (72-kD gelatinase/type IV collagenase = gelatinase A), MMP-3 (stromelysin-1), MMP-9, and tissue inhibitor of metalloproteinases-1 demonstrated that MMP-9 is localized exclusively in osteoclasts of the bone tissues from normal subjects and patients with rheumatoid arthritis or metastatic carcinoma whereas some osteoclasts are also labeled by anti-(MMP-1) antibody. Northern blot and in situ hybridizations of rheumatoid bone tissues using a RNA probe for MMP-9 exhibited strong signals for the mRNA within osteoclasts. MMP-9 depolymerized acid-insoluble polymers of type I collagen and digested collagen fibrils in the demineralized bone. The gelatinolytic activity of the proteinase was optimal at pH 7.5, but 50 to 80% of the full activity was retained at pH 5.5 to 6.0. It was also 90% active in the presence of 100 mM Ca2+. Degradation of acid-soluble and -insoluble type I collagens by MMP-9 was enhanced at higher concentrations of Ca2+. The zymogen of MMP-9 was activated up to approximately 85% of full activity by incubation at pH 2.3. CONCLUSIONS: These results demonstrate that MMP-9 is produced by osteoclasts in the human bone tissues and suggest that it can degrade bone collagens in concert with MMP-1 and cysteine proteinases in the subosteoclastic microenvironment. This proteinase may play a role in the normal bone remodeling and pathologic bone resorption in the human diseases.
1283056 Study of the major phenotype of large granular T-cell lymphoproliferative disorder. 1992 Nov Six cases of large granular T-cell lymphoproliferative disorder with a selected immunophenotype (CD3+, CD4-, CD8+, CD16+) were studied to characterize a homogeneous group of patients. It was found that most of these patients did not exhibit the clinical features frequently described in large granular T-cell lymphoproliferative disorder--recurrent infection, rheumatoid arthritis, and splenomegaly. The laboratory tests usually positive in large granular T-cell lymphoproliferative disorder, including rheumatoid factor and anti-nuclear antibodies, also were frequently negative. The pathognomonic features were found to be neutropenia and large granular lymphocytosis with positive killer cell markers. All six cases showed T-cell receptor gene rearrangement that indicated a monoclonal proliferation of lymphoid cells, which were natural killer-like T cells by immunophenotyping. B cells were essentially absent in all cases. It should be emphasized that bone marrow aspirates are as informative as peripheral blood samples for the diagnosis of large granular T-cell lymphoproliferative disorder; indeed, phenotypes of blood and marrow in one case were identical in terms of percentages of markers. In this selected group of patients, the clinical courses were indolent with uncomplicated outcomes. In three patients, chemotherapy did not induce an obvious clinical response, but all patients' conditions remained stable with only supportive care.
8387962 Oxidative modification of inflammatory synovial fluid immunoglobulin G. 1993 Apr The release of highly reactive oxygen-derived products by activated phagocytic cells in inflammatory foci plays a major role in defense mechanisms against infection and in the generation of tissue injury. Oxidative modification of proteins in inflammatory foci may give rise to products that contribute to the perpetuation of inflammation. The present studies analyze the oxidative alterations of inflammatory synovial fluid immunoglobulin G (IgG). IgG was purified from the synovial fluids of five patients with rheumatoid arthritis and two patients with acute gouty arthritis by three sequential steps: gel filtration chromatography, immunoaffinity chromatography, and a final gel filtration chromatography step under dissociative conditions (4 M guanidine). The resulting protein peaks of > 150 kDa (pool I-1), 150 kDa (pools I-2 and II-2), and < 150 kDa (pools I-3 and II-3) were tested for the presence of a fluorescence profile distinctive of oxidized proteins, the peak corresponding to monomer IgG (pool II-2) was subjected to quantitative amino acid analysis, and the results were compared with a standard preparation of normal IgG oxidized with HOCl. In addition, the protein pools were tested for the presence of lipid peroxide products. The results indicate that a portion of the affinity-purified IgG formed high-molecular-mass covalently cross-linked aggregates as evidenced by its presence in the > 150-kDa pool after dissociatve gel filtration chromatography. Moreover, this fraction and the pool corresponding to monomer IgG (pool II-2) exhibited the fluorescence profile characteristic of oxidized proteins. Amino acid analysis of the monomer IgG fraction revealed decreases in the content of histidine, methionine, tyrosine, and cysteine, which were similar to the alterations measured in normal IgG oxidized by HOCl. The synovial fluid and standard oxidized IgG showed the presence of oxidative by-products of tyrosine (monochlorotyrosine) and cysteine (cysteic acid). The synovial fluid IgG yielded a novel component that was not present in the standard control or oxidized IgG. This component was partially identified by mass spectrometry. Finally, the smaller peptide fraction isolated from affinity-purified synovial fluid IgG (pools I-3 and II-3) only after the gel filtration chromatography step under dissociative conditions exhibited evidence of oxidative damage and the presence of high concentrations of thiobarbituric acid-reactive material (TBAR). These observations suggest that oxidative processes in inflammatory foci generate products derived from protein and lipids that may contribute to the self-perpetuation of inflammation.
8144907 Requirement of donor-derived stromal cells in the bone marrow for successful allogeneic bo 1994 Mar 15 MRL/MP-Ipr/Ipr (MRL/Ipr) mice possess radioresistant (9.5 Gy) abnormal stem cells and show a recurrence of autoimmune diseases within 5 mo of conventional allogeneic bone marrow transplantation. We recently have found that the MHC preference exists between hemopoietic stem cells and stromal cells; when bones are engrafted, donor-derived stromal cells present in the engrafted bones can migrate into the recipient bone marrows, which are replaced with both donor-derived stromal cells and hematopoietic cells. Based on these findings, we attempted to prevent the recurrence of autoimmune diseases in MRL/Ipr mice by the transplantation of both bone marrow cells and bone (as a source of stromal cells). MRL/Ipr mice were irradiated (8.5 Gy) and then reconstituted with C57BL/6 bone marrow cells plus bone grafts. The mice survived more than 48 wk after this treatment. Immunohistologic studies revealed that the mice were completely free from both lymphadenopathy and autoimmune diseases such as lupus nephritis and rheumatoid arthritis. Sera from these mice showed normal levels of circulating immune complexes and rheumatoid factors. Normal functions of both T cells and B cells were noted. Abnormal T cells such as Thy-1+B220+ cells present in nontreated MRL/Ipr mice could not be seen in the thus-treated mice. In addition, to our surprise, spleen cells from treated mice showed completely normal in vitro primary anti-SRBC responses. These results indicate that stromal cells in allogeneic bone marrow transplantation play a crucial role not only in the prevention of graft failure but also in the successful cooperation among APCs, T cells, and B cells. Although MRL/Ipr mice are radiosensitive and usually die of interstitial pneumonia or fatty liver due to the side effects of radiation, it should be noted that this strategy allows a reduction in the radiation dose (9.5 Gy-->8.5 Gy), and that these mice can survive more than 48 wk without showing any symptoms of autoimmune diseases.
8046238 Chemical and serologic characterization of human lambda VIII light chains. 1994 Aug 15 The primary structural features and serologic properties of a newly recognized human lambda light (L) chain V region subgroup (V lambda VIII) were elucidated through study of two monoclonal L chains, Bence Jones proteins HAG and BIV. The V region amino acid sequences of these components were highly homologous to each other and to that deduced from the prototypic V lambda VIII cDNA, Humla8f10, which encodes the L chains of the IgM lambda rheumatoid factor HAF10. Proteins HAG and BIV could be classified as members of the V lambda VIII subgroup and distinguished from L chains of the V lambda I, V lambda II, V lambda III, V lambda IV, and V lambda VI subgroups on the basis of amino acid sequence. In addition to distinctive residues found within the V lambda gene-encoded portion of the molecules, L chains HAG, BIV, and HAF10 contained remarkably different second complementarity-determining regions (CDR2) that consisted of 11 residues, rather than the seven typically found among members of the other five V lambda subgroups. This elongated structure would presumably impart to the ligand-binding site of lambda VIII molecules a markedly different canonical structure compared with those of lambda I, lambda II, lambda III, lambda IV, and lambda VI L chains. By using Bence Jones protein HAG as an immunogen, we obtained polyclonal and monoclonal anti-V lambda VIII subgroup-specific Abs that were used to identify and quantify lambda VIII-related molecules in normal and pathologic states. Among the Ig lambda components present in the serum of normal individuals, approximately 3% had lambda VIII L chains, a frequency comparable to that found among monoclonal Ig lambda proteins or surface(s) Ig lambda+ cells obtained from patients with malignant plasma cell- or B cell-related disorders, respectively. In contrast, lambda VIII L chains were detected on approximately 19% of monoclonal IgM lambda rheumatoid factors produced by B cell lines established from PBLs or synovial cells from patients with rheumatoid arthritis. The results of our studies provide new information on the structural and immunochemical features of lambda VIII L chains and the possible functional importance of the human V lambda VIII subgroup.
1472126 Association of dry eyes and dry mouth with anti-Ro/SS-A and anti-La/SS-B autoantibodies in 1992 Dec OBJECTIVE: To evaluate the extent to which seemingly healthy, mature adults with mild symptoms of dry eyes or dry mouth share the immunologic features found in patients with Sjögren's syndrome. METHODS: Of 705 subjects in Malmö, Sweden (age range 52-72 years) who responded to a questionnaire, 35% reported some symptoms of dry eyes or mouth. A random subgroup of the symptomatic subjects (n = 77) and an age- and sex-matched control group from among the asymptomatic subjects (n = 32) were evaluated objectively by serologic testing and by various measures of exocrine gland function. RESULTS: The symptomatic subjects had relatively impaired exocrine gland function and elevated levels of anti-Ro and anti-La (1.54-2.88-fold increase compared with the asymptomatic subjects, 95% confidence interval [CI] 1.41, 4.03). The 2 autoantibodies correlated with each other (r = 0.64, 95% CI 0.49, 0.78) as well as with selected clinical measures of glandular function. CONCLUSION: The association between self-reported symptoms of dry eyes or dry mouth and anti-Ro and anti-La, found in more than one-third of mature adults in this study, suggests that the immune abnormalities and exocrine gland dysfunction found in Sjögren's syndrome affect a substantial proportion of the general population.
8978961 Interleukin 6: a possible marker of disease activity in adult onset Still's disease. 1996 Nov OBJECTIVE: Adult onset Still's disease (AOSD) is an inflammatory disorder with elevated serum acute phase proteins. Interleukin-6 is a major contributor to the acute phase response. We therefore examined the serum levels of CRP, SAA and interleukin-6 in active and inactive AOSD. RESULTS: Active patients had significantly elevated CRP, SAA, and interleukin-6 values. After steroid treatment a marked reduction was observed in all three parameters. There was a close kinetics on the fluctuations of CRP and SAA, but not on IL-6. CONCLUSION: Acute phase proteins and IL-6 are useful markers of disease activity in AOSD.
8913094 [A case of Sjögren's syndrome complicated by membranous nephropathy]. 1996 Sep A case of Sjögren's syndrome (SjS) complicated by membranous nephropathy (MN) is presented. A 50-year-old female was admitted to Toho University Hospital because of overt proteinuria (5g/day). She had xerotic keratitis in addition to a renal disorder, and laboratory data showed positive anti-nuclear antibody (ANA) and anti-SSA antibody. The specimens from renal biopsy revealed mild thickening of the glomerular basement membrane under light microscopy, positive IgG along the capillary walls revealed by immunofluorescence, and sparse and irregular subepithelial electron dense deposits seen under electron microscopy. No interstitial changes were observed. From these findings, she was diagnosed as having SjS complicated by MN. Proteinuria gradually decreased with a reduction in serum levels of ANA and anti-SSA antibody following corticosteroid therapy. Although renal interstitial lesions occasionally develop in patients with SjS, glomerular changes, especially MN, are very rare. We suspect that immunocomplexes, such as anti-SSA antibody, revealed in SjS patients could be responsible for the glomerular lesions, leading to MN.
8546739 Treatment of xerostomia with polymer-based saliva substitutes in patients with Sjögren's 1996 Jan OBJECTIVE: To determine the efficacy of 3 types of polymer-based saliva substitutes in reducing oral dryness in patients with Sjögren's syndrome (SS). METHODS: Subjective efficacy of 3 different saliva substitutes (determined by self-administered questionnaire) was evaluated in a double-blind, placebo-controlled trial in 43 patients with primary and secondary SS. High-viscosity versus low-viscosity xanthan gum-based saliva substitutes were also compared in 33 SS patients. Salivary flow rates (SFR) were determined to examine correlations between the SFR and the subjective efficacy of the saliva substitute. RESULTS: Neither the saliva substitutes nor the placebo was truly effective. Preference for a particular saliva substitute over placebo was equally distributed among the 3 types of substitutes. The SFR of patients who preferred polyacrylic acid-based saliva substitutes was lower than that in patients who preferred the porcine mucin-based substitute (P < 0.05). Patients whose oral dryness was reduced by low-viscoelastic substitutes had a low stimulated SFR ( < 0.20 ml/minute; P < 0.05). CONCLUSION: The optimal properties of a saliva substitute are not the same for all patients with SS, but are dependent on such parameters as the individual SFR. Thus, to determine the best saliva substitute for a particular patient, it is necessary to have the patient try a number of substitutes of different viscoelastic properties.
8531369 [Primary biliary cirrhosis in patients with Sjögren's syndrome]. 1995 Oct Primary biliary cirrhosis (PBC) is one of the most frequent hepatic diseases associated with Sjögren's syndrome (SS), its reported incidence ranging from 3% to 9%. There is much association between SS and PBC in the pathogenesis. In both diseases, autoimmunity seems to be directed toward the ductal epithelial cells. Epstein Barr Virus may contribute to PBC, as well as SS. PBC associated with SS tends to be asymptomatic and to be in an early stage in histologically. Antimitochondrial antibody (AMA) is the most sensitive indicator of PBC in primary SS. When SS patients have an elevated alkaline phosphatase level, it is necessary to examine AMA and to perform liver biopsy.
7722607 Silicone breast implants and long-term health effects: when are data adequate? 1995 Apr The epidemiological literature examining the possible association between silicone breast implants and breast cancer or rheumatological conditions or diseases is far greater today than it was when, in early 1992, FDA determined that the data were not adequate for the assessment of their safety. A literature data base exists for assessing the magnitude of risk for certain diseases that might be associated with silicone breast implantation and for narrowing the uncertainty in those estimates. The studies reported in this series make a major contribution to that database. As for future research needs, some general observations can be made. First, it is likely that completed, ongoing and planned studies will prove more than adequate in accurately delineating any cancer risks that might be associated with breast implantation. Second, the risks of developing scleroderma will also be reasonably well established. Further study may be desirable for other specific connective tissue diseases and for connective tissue disease considered as a whole.
7578884 Cytokine gene and CD25 antigen expression by peripheral blood T cells from patients with p 1995 We studied mononuclear cell subsets in 17 patients with primary Sjögren's syndrome (PSS) and in 11 normal controls by flow cytometry. We found a decreased percentage of CD4+ cells (p = 0.027) and a higher percentage of CD8+ cells in patients as compared to controls. In both, CD4+ cells and CD8+ cells, CD25 antigen was overexpressed (p = 0.005 and p = 0.025, respectively as compared to controls). We then measured spontaneous mRNA cytokine expression by T cells from 7 PSS patients and 5 normal controls by coupled reverse transcription-polymerase chain reaction. We found spontaneous mRNA expression for IFN-gamma, IL-10, IL-13 as well as for CD25. Our results suggest an overall T cell activation in PSS patients and provides evidence of a T cell cytokine regulatory imbalance which may play a role in the pathogenesis of this disease.
7868806 Acquired nephrogenic diabetes insipidus secondary to distal renal tubular acidosis and nep 1994 Sep A 52-year-old woman was referred to our hospital because of 16-year history of polyuria and polydipsia. Hyposthenuria, hyperchloremic metabolic acidosis and the inabilities to acidify the urine after acid-loading test and to concentrate the urine in responses to water-deprivation and antidiuretic hormone administration allowed us to diagnose renal tubular acidosis and nephrogenic diabetes insipidus. Radiographic examinations revealed bilateral nephrocalcinosis. The patient was also found to have clinical and laboratory findings characteristic for Sjögren's syndrome. Thus the longstanding, poorly monitored distal renal tubular acidosis associated with Sjögren's syndrome was considered to result in very rare renal complications-nephrocalcinosis and nephrogenic diabetes insipidus. In patients with renal tubular acidosis and/or nephrogenic diabetes insipidus of unknown etiology, therefore, Sjögren's syndrome should be considered as one of primary disorders.
8468823 [A case of primary pulmonary lymphoma associated with Sjögren syndrome and IgM monoclonal 1993 Jan A 70-year-old man was admitted for evaluation of an abnormal shadow on his chest X-ray film, consisting of a mass containing an air bronchogram. He was also found to have a monoclonal gammopathy (IgM kappa type) and Sjögren syndrome. Open lung biopsy was performed with the suspicion of primary pulmonary lymphoma or pseudolymphoma. Southern blot analysis of the tissue revealed clonal rearrangements of immunoglobulin gene, supporting the diagnosis of B-cell lymphoma. Using conventional immunoperoxidase staining (PAP) method, the monoclonality in the tissue specimen is sometimes quite difficult to prove. Southern blot analysis, however, gives more accurate and reliable results. The analysis of immunoglobulin gene rearrangements is quite useful in determining the presence or absence of monoclonality in a specimen in cases of suspected lymphoproliferative disease such as primary pulmonary lymphoma and pseudolymphoma. We strongly recommend the use of Southern blot analysis in making the diagnosis of lymphoproliferative disease.
1306596 [Lupus, sicca syndrome and chronic interstitial nephritis. Apropos of a case]. 1992 Nov 30 A female patient from the French Antilles developed renal failure due to pure chronic interstitial nephritis six months after the onset of systemic lupus erythematosus (SLE) for which she was taking hydroxychloroquine. Over time, results of biologic tests became suggestive of concomitant Gougerot-Sjögren syndrome, but neither the clinical nor the histologic findings were consistent with this diagnosis. The diagnosis of overlap syndrome between SLE and Gougerot-Sjögren syndrome was established only six years later when the patient developed ocular and oral sicca syndrome with enlargement of the parotid glands.
8915704 A human T-cell lymphotropic virus type-I carrier with chronic renal failure, aplastic anem 1996 Sep A 53-year-old female infected with human T lymphotropic virus type-I (HTLV-I) suffered from chronic renal failure, aplastic anemia, myelopathy, uveitis, Sjögren's syndrome and Weber-Christian disease. Although HTLV-I antibody was negative in cerebrospinal fluid, she was diagnosed as HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) based on clinical and histological findings. Though to date there is no direct evidence, other complications have also been reported to be HTLV-I related diseases. This case provided the unique opportunity to observe various HTLV-I related diseases.
8531344 [Molecular mechanism on Sjögren's syndrome]. 1995 Oct Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration into lachrymal and salivary glands leading to symptomatic dye eyes and mouth. Immunohistological studies have clarified that the majority of infiltrating lymphocytes around the lachrymal glands and labial salivary glands are CD4 positive alpha beta T cells. To analyze the nature of T cells in lachrymal glands and labial salivary glands, we examined TCR V beta genes of infiltrating T cells into both glands from SS patients, using PCR-SSCP and sequencing methods. The results showed the following two findings. 1) Some of T cells infiltrating in both glands expand clonally, suggesting that these cells proliferate by antigen-driven stimulation. 2) The common T cells accumulated in lachrymal and labial salivary glands. In conclusion, autoreactive T cells in lips and eyes should recognize the same epitopes of autoantigen in individual patients with SS. Further analysis on autoantigen using T cell lines from labial salivary glands supports the notion that Ro/SS-A 52 kD is a possible autoantigen recognized by autoreactive T cells.
7864694 Collagenase in Sjögren's syndrome. 1994 Dec OBJECTIVE: To study collagenase production in labial salivary glands in patients with Sjögren's syndrome (SS). METHODS: Collagenases were localised in labial salivary glands by immunohistochemistry. Collagenase activity against triple helical type I collagen monomers in stimulated saliva was measured using sodium dodecyl sulphate polyacrylamide gel electrophoresis and laser densitometry; tissue inhibitor metalloproteinase (TIMP) was measured by enzyme linked immunosorbent assay. RESULTS: Cells containing collagenase of matrix metalloproteinase (MMP)-1 type were more frequent and more intensely staining in SS than in healthy glands. Only SS saliva contained functional enzyme (11.7 (6.8) x 10(-6) IU/1). Cells containing MMP-8 type neutrophil collagenase were not found in situ, which was in accordance with sialochemical findings/doxycycline inhibition studies. TIMP was found in both SS and normal saliva. CONCLUSIONS: Fibroblast, but not neutrophil type, collagenase is synthesised, secreted, and subsequently activated, but is not inhibited by TIMP in labial salivary glands or saliva in SS. Collagenase may destroy glandular and salivary duct tissue and perturb factors influencing the morphogenetic extracellular matrix.
8195531 Clinical significance of maternal anti-Ro/SS-A antibodies in children with isolated heart 1994 Jun OBJECTIVES: We studied 30 consecutive children with isolated heart block to assess the clinical impact of the presence of maternal anti-Ro/SS-A antibodies for isolated heart block. BACKGROUND: Isolated heart block in children, often associated with maternal autoimmune disease leading to anti-Ro/SS-A auto-antibody production, is an infrequent but potentially lethal disorder. METHODS: Thirty children with isolated heart block were studied with respect to medical history and electrocardiographic (ECG) analysis. The presence of anti-Ro/SS-A antibodies was determined in the maternal serum. We also examined the ECGs of all brothers and sisters of the patients for conduction abnormalities. RESULTS: Twenty-one of the 30 children had an anti-Ro/SS-A-positive mother (group A); the other 9 children had an anti-Ro/SS-A-negative mother (group B). Comparison of the clinical data from both mothers and children revealed that these two groups differed significantly with respect to the following: Prenatal diagnosis and obstetric complications occurred more often in group A, whereas progression to complete block, QRS width > 0.08 s, premature ventricular contractions and ventricular standstills > 4.5 s occurred more often in group B. In addition, mothers of children in group A reported more spontaneous abortions. All siblings of children in groups A and B had normal ECGs, excluding a subclinical form of heart block. CONCLUSIONS: Two types of heart block can be recognized: Congenital heart block is associated with maternal anti-Ro/SS-A antibodies and numerous obstetric and neonatal complications. It is diagnosed prenatally or at birth and is usually complete at onset and probably has a substantial recurrence risk. Heart block that is acquired later in life is not associated with maternal autoimmunity and has no risk for recurrence. It often presents as a partial block but progresses to complete block in time.