Multiple Nuclear Dots Research Articles

原発性胆汁性肝硬変と自己抗体

Fifty years have passed since anti-mitochondrial antibodies were found in patients with primary biliary cirrhosis (PBC). PBC is an autoimmune hepatic disease in which 85-90% of patient antibodies bind to mitochondrial antigens that include pyruvate dehydrogenase complex (PDC)-E2 and other members of the oxaloacid dehydrogenase family. In addition, indirect immunofluorescence (IIF) assays utilizing HEp-2 cell substrates have been used to identify anti-centromere antibodies in 20-30% of PBC sera. These antibodies are generally easily recognized, however, anti-nuclear envelope and anti-multiple nuclear dot antibodies are occasionally more difficult to recognize with certainty by IIF. The use of enzyme linked immunosorbent assays that utilize recombinant gp210 (an autoantigen of the nuclear envelope) and/or sp100 (a protein target represented by multiple nuclear dots) should be particularly considered in anti-mitochondrial antibody negative PBC sera. Although the clinical significance of these antibodies still remains to be determined, there is evidence that the existence of anti-gp210 antibodies are related to poorer prognosis and more aggressive disease progression.

Nuclear envelope protein autoantigens in primary biliary cirrhosis

Antinuclear antibodies are detectable in approximately 50% of subjects with primary biliary cirrhosis (PBC). Most clinical laboratories use indirect immunofluorescence microscopy to detect antinuclear antibodies and two labeling patterns that predominate in PBC are nuclear rim and multiple nuclear dots. Antibodies giving these patterns most often recognize nuclear envelope protein gp210 and nuclear body protein sp100, respectively. Fewer subjects with PBC have autoantibodies giving nuclear rim labeling that recognize nucleoporin p62 and LBR. Gp210 is an integral protein localized to the nuclear pore membranes. Approximately 25% of subjects with PBC have detectable serum anti-gp210 antibodies. The vast majority of anti-gp210 antibodies from patients with PBC recognize a stretch of only 15 amino acids in the carboxyl-terminal tail that faces the nuclear pore complex. Enzyme-linked immunosorbent assays using either recombinant protein expressed in bacteria or chemically synthesized polypeptides have been established to reliably detect these autoantibodies. Although initial studies did not find a correlation between the presence of anti-gp210 antibodies and prognosis in PBC, recent data suggest that the presence of antinuclear envelope protein antibodies correlate with an unfavorable disease course and more rapid progression.

Comparison of Two ELISA Assays for Anti‐Sp100 Determination

Antibodies to Sp100 have been described not only in primary biliary cirrhosis (PBC), but also in other diseases. Two assays for detection of Sp100 levels by enzyme-linked immunosorbent assay (ELISA) have been compared in a cohort of patients from our area: (a) Sp100 kit produced by IMTEC, Immunodiagnostica GmbH, and (b) Quanta Lite Sp100 kit produced by INOVA Diagnostics. We analyze here the correlation between the two assays and compare their efficiency in diagnosing PBC. We also comment on the exceptions derived from reactivity with other diseases. We studied 78 sera by IIF with the typical multiple nuclear dots (MND) pattern from patients who suffered from PBC, hepatopathies different from PBC, systemic lupus erythematosus (SLE), other connective tissue diseases (CTD), skeletal diseases, lung diseases, hematological disorders, a miscellaneous group, and a healthy IIF negative control group. The tests work equally well despite their different quantification system: (a) it is based on a standard curve; and (b) it is based on a single-point antigen-specific calibration. Some discrepancies could be explained by differences in the immunodominant epitope used in the ELISA. The main finding of this study is that the presence of MND/Sp100-positive antibodies were detected not only in hepatic diseases, mainly PBC, but also in other clinical conditions, confirmed by both tests. Diagnosis of PBC must be established in the right clinical context, because other diseases recognizing the same epitope, mainly SLE, may also show high Sp100 levels. Sera from PBC patients with antimitochondrial antibodies (AMA) showed higher anti-Sp100 than the AMA-negative group.

Antinuclear antibodies giving the ‘multiple nuclear dots’ or the ‘rim‐like/membranous’ patterns: diagnostic accuracy for primary biliary cirrhosis

Serum antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' patterns are frequently detected by indirect immunofluorescence on HEp-2 cells in patients with primary biliary cirrhosis. To assess the accuracy of multiple nuclear dot and rim-like/membranous antinuclear antibodies for the diagnosis of primary biliary cirrhosis. Sera from 4371 consecutive patients referred to our laboratory were analysed under code for antinuclear antibodies testing by indirect immunofluorescence on HEp-2 cells. Review of the clinical records of the 4371 patients allowed identification of 101 patients with antimitochondrial antibody-positive primary biliary cirrhosis and 22 with antimitochondrial antibody-negative variant. Multiple nuclear dot and/or rim-like/membranous patterns were found in 59 (1.3%) of the 4371 patients: 31 antimitochondrial antibody-positive primary biliary cirrhosis, 17 antimitochondrial antibody-negative primary biliary cirrhosis and 11 non-primary biliary cirrhosis. The specificity for primary biliary cirrhosis of both the antinuclear antibodies pattern was 99%. Positive predictive value and likelihood ratio for a positive test were 86% (95% CI: 72.7-94) and 221 (95% CI: 91.7-544) for multiple nuclear dot, 79% (95% CI: 62.2-90.1) and 132 (95% CI: 56.8-312.7) for rim-like/membranous, respectively. Multiple nuclear dot and rim-like/membranous antinuclear antibodies are rare findings. Their positivity strongly suggests the diagnosis of primary biliary cirrhosis, irrespective of antimitochondrial antibody status. The high specificity for primary biliary cirrhosis makes them a useful diagnostic tool especially in antimitochondrial antibody-negative patients.

Diagnostic accuracy of anti-nuclear antibodies giving a multiple nuclear dots (MND) or a membranous (RL/M) pattern in primary biliary cirrhosis

Diagnostic accuracy of anti-nuclear antibodies giving a multiple nuclear dots (MND) or a membranous (RL/M) pattern in primary biliary cirrhosis

Do antinuclear antibodies in primary biliary cirrhosis patients identify increased risk for liver failure?

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease with a variable clinical course. Identification of serologic markers associated with increased risk of liver failure would assist in management of PBC patients. The objective of this study was to identify antinuclear antibody (ANA) markers that may be used to predict PBC outcome. Indirect immunofluorescence was used to identify ANAs in 492 PBC patients. chi2 and Kaplan-Meier analyses were used to examine the association between ANAs and liver failure. A greater percentage of ANA-positive, compared to ANA-negative, PBC patients developed liver failure (41% vs 25%, P = .005). The presence of anti-centromere antibodies was associated with liver failure (anti-centromere antibody positive vs negative, 58% vs 33%, P = .001). The time to liver failure was shorter in ANA-positive, compared with ANA-negative, patients (log rank score 5.8, P = .02). After 8.9 years (the median follow-up for patients without liver failure), 68% of ANA-positive and 81% of ANA-negative patients were free of liver failure. Anti-centromere antibodies were also associated with a shorter time to liver failure (log rank score 8.4, P = .004). After 8.9 years, 52% of anti-centromere antibody positive and 74% of anti-centromere antibody negative patients were without liver failure. ANAs in general, and anti-centromere antibodies in particular, are associated with liver failure in PBC. PBC patients with ANAs may be candidates for treatment with experimental therapies to prolong the interval between diagnosis and liver failure. ANA-negative patients, who appear to have a relatively benign clinical course, should perhaps be treated with ursodeoxycholic acid alone.

Case Report: Histologic Features of Steatohepatitis in Patients with a Clinical Diagnosis of Autoimmune Cholestasis

Nonalcoholic steatohepatitis (NASH) is a disease included in the spectrum of nonalcoholic fatty liver disease, which is able to continue progression toward cirrhosis (1). The definition of NASH relies on the common exclusion of significant alcohol use (<20 g/day) and the characteristic histological lesions include some degree of steatosis in addition to mixed lobular inflammation and hepatocyte damage (ballooning degeneration with or without Mallory’s hyaline) (2). NASH has been found in patients suffering from chronic hepatitis C (3) and also in other forms of liver diseases, such as chronic hepatitis B, autoimmune hepatitis, drug-induced liver disease, and α-1 antitrypsin deficiency (4). Primary biliary cirrhosis (PBC) should be considered when patients show a biochemical and histological cholestatic pattern along with positive serum antimitochondrial antibodies (AMA), including immunoblot studies, or PBC-specific antinuclear antibodies (ANA), mainly anti-SP100 and anti-GP210 (5), while patients showing a cholestatic pattern together with negative AMA and positive ANA (different from rim-like or multiple nuclear dots) need to be classified as having autoimmune cholangitis (AIC) (5, 6). Differences found between both groups according to biochemical or histological features are minimal. Indeed, histopathologic features of both entities consist of characteristic interlobular and septal bile ducts lesions (florid duct lesion), cholestasis, ductular proliferation, portal and periportal hepatitis, usually mild

Serum Immunological Profile in Patients with Chronic Autoimmune Cholestasis

To compare patients who had biochemical and histological features of chronic autoimmune cholestasis (CAIC) using serological autoantibody profiling. Patients (n = 174 CAIC; 79 AMA(-) and 95 AMA(+)) were profiled for the following antibodies: antinuclear antibodies (ANAs), antimitochondrial antibodies (AMAs), antismooth muscle actin (SMA, mainly F-actin), antiperinuclear cytoplasmic neutrophil antibodies (pANCAs), anti-SP100, anti-GP210, anti-M2 (2-oxo-acid dehydrogenase complexes), and antisoluble liver antigen (SLA). Liver specimens were reviewed according to staging, biliary interface activity, lobular hepatitis, granulomas, cholestasis, and florid ductal lesion. In patients who were AMA(-) by indirect immunofluorescence (IIF), 34.6% were positive for anti-M2 by immunoblotting. In 49 definitively AMA(-) patients, 24 (48.9%) showed ANA-primary biliary cirrhosis (PBC)-related antibodies (rim-like, multiple nuclear dots, anti-SP100, or anti-GP210). There were no differences in immunological, biochemical, or histopathological features between IIF-AMA(+) patients and AMA(-) patients with anti-M2 or ANA-PBC-related antibodies. AIH-related autoantibodies were found in 13 patients (7.5%). Patients with AMAs or ANA-PBC-related antibodies had higher IgM levels, whereas patients with antibodies highly specific for AIH had higher AST, bilirubin, and IgG levels, and AIH scores, and higher grades of lobular hepatitis. Overall, three distinct categories of patients were observed: AMA(+) or AMA(-) patients with ANA-PBC-related antibodies; AMA(-) patients with non-PBC-related ANAs; and patients with AIH-related antibodies together with serum PBC markers. Since these three groups had immunological, biochemical, and histopathological differences, they ought to be considered as separate clinical subentities rather than as merely AMA(-) or AMA(+) patients with autoimmune cholestasis.

Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis.

The clinical impact of antinuclear antibodies in primary biliary cirrhosis is uncertain. We analyzed in detail the antinuclear antibodies reactivity of primary biliary cirrhosis patients and correlated the fine specificities observed with clinical, biochemical, and immunologic parameters. A total of 96 consecutive primary biliary cirrhosis patients and 283 pathologic controls were studied. To dissect the fine antinuclear antibodies specificities we used different techniques, such as indirect immunofluorescence on cryostat tissue sections and cell culture (HEp-2 cells), counterimmunoelectrophoresis with thymus and spleen extracts, ELISA assays with recombinant Sp100 and purified gp210 and Lamin B receptor, and immunoblot with several recombinant nuclear and cytoplasmic antigens. Antinuclear antibodies were detected in 53% of patients, with the following hierarchy of specificities: 27% anti-Sp100, 16% "multiple nuclear dots," 16% anti-gp210, 16% anti-centromere, 7% XR1, 6% anti-lamin B receptor, 5% anti-SS-A/Ro, 5% anti-ribonucleoprotein, 4% XR2, 2% anti-SS-B/La, 2% perinuclear antineutrophil cytoplasmic antibodies, and 1% anti-double-stranded deoxyribonucleic acid. Several patients showed multiple specificities. The "multiple nuclear dots" pattern was detected more often in antimitochondrial antibodies negative patients. In particular, primary biliary cirrhosis specific antinuclear antibodies (anti-Sp100, anti-gp210, and anti-lamin B receptor) were detected in nine of 13 antimitochondrial negative primary biliary cirrhosis cases. Anti-gp210 was more frequent in patients with more pronounced cholestasis and more impaired liver function. Antinuclear antibodies reactivities are present in more than half of primary biliary cirrhosis patients and target diverse autoantigens located in distinct subnuclear structures. Anti-gp210 identifies a subgroup of primary biliary cirrhosis patients with more serious liver disease. Positivity for anti-Sp100, anti-gp210, and anti-lamin B receptor, either alone or in combination, may act as a serologic marker of antimitochondrial antibodies negative primary biliary cirrhosis.

Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis

Objectives The clinical impact of antinuclear antibodies in primary biliary cirrhosis is uncertain. We analyzed in detail the antinuclear antibodies reactivity of primary biliary cirrhosis patients and correlated the fine specificities observed with clinical, biochemical, and immunologic parameters. Methods A total of 96 consecutive primary biliary cirrhosis patients and 283 pathologic controls were studied. To dissect the fine antinuclear antibodies specificities we used different techniques, such as indirect immunofluorescence on cryostat tissue sections and cell culture (HEp-2 cells), counterimmunoelectrophoresis with thymus and spleen extracts, ELISA assays with recombinant Sp100 and purified gp210 and Lamin B receptor, and immunoblot with several recombinant nuclear and cytoplasmic antigens. Results Antinuclear antibodies were detected in 53% of patients, with the following hierarchy of specificities: 27% anti-Sp100, 16% “multiple nuclear dots,” 16% anti-gp210, 16% anti-centromere, 7% XR1, 6% anti-lamin B receptor, 5% anti–SS-A/Ro, 5% anti-ribonucleoprotein, 4% XR2, 2% anti–SS-B/La, 2% perinuclear antineutrophil cytoplasmic antibodies, and 1% anti–double-stranded deoxyribonucleic acid. Several patients showed multiple specificities. The “multiple nuclear dots” pattern was detected more often in antimitochondrial antibodies negative patients. In particular, primary biliary cirrhosis specific antinuclear antibodies (anti-Sp100, anti-gp210, and anti-lamin B receptor) were detected in nine of 13 antimitochondrial negative primary biliary cirrhosis cases. Anti-gp210 was more frequent in patients with more pronounced cholestasis and more impaired liver function. Conclusions Antinuclear antibodies reactivities are present in more than half of primary biliary cirrhosis patients and target diverse autoantigens located in distinct subnuclear structures. Anti-gp210 identifies a subgroup of primary biliary cirrhosis patients with more serious liver disease. Positivity for anti-Sp100, anti-gp210, and anti-lamin B receptor, either alone or in combination, may act as a serologic marker of antimitochondrial antibodies negative primary biliary cirrhosis.

Clinical Significance of Anti-Multiple Nuclear Dots/Sp100 Autoantibodies

Background: Autoantibodies against discrete variable-sized dots observed in HEp2 cells by indirect immunofluorescence (IIF) test, called multiple nuclear dots (MND), have been closely associated with primary biliary cirrhosis (PBC). Some authors have argued that this antibody is also present in connective tissue diseases or liver diseases other than PBC as autoimmune chronic active hepatitis, particularly of the cholestatic type. We studied an unselected group of patients routinely tested for autoantibodies and positive for the MND pattern and tried to establish the correlation between the presence of this antibody and their diagnosis. Methods: A commercial ELISA test, using a recombinant 26 r kD truncated sequence of the Sp100 protein, corresponding to an immunodominant molecular region, was used to assess the clinical correlation of these autoantibodies in 110 patients showing an anti-MND immunofluorescence pattern. Results: One-hundred-and-ten patients were MND positive by IIF. Of these, 100 were Sp100 positive by ELISA. In the Sp100 positive group, 34 had a diagnosis of PBC (30 definite and 4 suspected) while 15 patients had a non-PBC hepatopathy. Unexpectedly, 13 of the MND/Sp100 positive pattern corresponded to systemic lupus erythematosus (SLE) patients and 5 cases to collagen diseases. Another divergence with previous reports was that 34 of the positive patients showed very heterogeneous clinical pictures, different from hepatopathies or collagen diseases. Conclusions: Anti-Sp100 antibodies can be found in many clinical conditions. Testing for MND/Sp100 positivity is useful for the diagnosis of PBC, but only when the right clinical context is present. Other diseases cannot be excluded in first line SLE.

Anti-multiple nuclear dots (anti-MND) and anti-SP100 antibodies in hepatic and rheumatological disorders.

Multiple nuclear dots pattern has been described in primary biliary cirrhosis and, less often, in rheumatological disorders. Sp100 is the major antigen of multiple nuclear dots. We evaluated prevalence and diagnostic significance of multiple nuclear dots and anti-Sp100 reactivity both in hepatic and rheumatological diseases. A series of 283 consecutive liver patients (89 primary biliary cirrhosis, 12 primary sclerosing cholangitis, 85 autoimmune hepatitis, 97 hepatitis C virus-related chronic liver disease) and of 89 consecutive rheumatological cases were evaluated. Presence of multiple nuclear dots was assessed by indirect immunofluorescence on HEp-2 cells, anti-Sp100 reactivity by ELISA with recombinant protein. Multiple nuclear dots were detected in 20 patients (7%) with liver disease (of whom 15 with primary biliary cirrhosis), and in eight patients (9%) with rheumatological disorders. Anti-Sp100 was detected in 45 liver patients (16%), of whom 30 with primary biliary cirrhosis, but in only two with rheumatological disorders (2%) (P =0.0004). The concordance between multiple nuclear dots and anti-Sp100 in liver and rheumatological patients was 90% and 25% (P=0.0018), respectively. Among 89 consecutive patients with primary biliary cirrhosis, multiple nuclear dots and anti-Sp100 were present in 17% and 34%, respectively (P=0.0152). Anti-Sp100 positivity was associated with older age and higher gamma-globulin levels. Multiple nuclear dots are similarly observed in liver and rheumatological patients. In contrast, anti-Sp100 is more frequent in liver patients and is significantly more often detected in primary biliary cirrhosis, of which it can be regarded as a highly specific serological marker. The antigenic target of multiple nuclear dots in most rheumatological patients is other than Sp100.

A Negative Regulator of Telomere-Length Protein TRF1 Is Associated with Interstitial (TTAGGG)n Blocks in Immortal Chinese Hamster Ovary Cells

Telomeres of mammalian chromosomes are composed of long tandem repeats (TTAGGG)n which bind in a sequence-specific manner two proteins—TRF1 and TRF2. In human somatic cells both proteins are mostly associated with telomeres and TRF1 overexpression resulting in telomere shortening. However, chromosomes of some mammalian species, e.g., Chinese hamster, have large interstitial blocks of (TTAGGG)n sequence (IBTs) and the blocks are involved in radiation-induced chromosome instability. In normal somatic cells of these species chromosomes are stable, indicating that the IBTs are protected from unequal homologous recombination. In this study we expressed V5-epitope or green fluorescent protein (GFP)-tagged human TRF1 in different lines of mammalian cells and analyzed distribution of the fusion proteins in interphase nucleus. As expected, transient transfection of human (A549) or African green monkey cells with GFP-N-TRF1 or TRF1-C-V5 plasmids resulted in the appearance in interphase nuclei of multiple faint nuclear dots containing GFP or V5 epitope which we believe to represent telomeres. Transfection of immortalized Chinese hamster ovary (CHO) cell line K1 which have extremely short telomeres with GFP-N-TRF1 plasmid leads to the appearance in interphase nuclei of large GFP bodies corresponding in number to the number of IBTs in these cells. Simultaneous visualization of GFP and IBTs in interphase nuclei of transfected CHO-K1 cells showed colocalization of both signals indicating that expressed TRF1 actually associates with IBTs. These results suggest that TRF1 may serve as general sensor of (TTAGGG)n repeats controlling not only telomeres but also interstitial (TTAGGG)n sequences.

A Novel Antibody Directed Against a Three‐Dimensional Configuration of a 95‐kDa Protein in Patients with Autoimmune Hepatic Diseases

Sera from patients with primary biliary cirrhosis recognize various cellular components, such as mitochondria, centromere, nuclear envelope, and multiple nuclear dot antigens. There also appears to be a novel antibody reacting with a particular protein in these sera. The presence of this antibody was investigated by double immunodiffusion using rat liver cytoplasmic antigens, by immunoprecipitation of [35S]-methionine labelled HeLa cell extracts, and by immunoblot using disrupted HeLa cell extracts. Test sera were obtained from 491 patients with various liver diseases. Nine of the 491 sera were found to react with a 95-kDa protein as determined by immunoprecipitation of [35S]-methionine labelled HeLa cell extracts and by double immunodiffusion using a rat liver microsomal preparation. However, these same nine sera showed no reaction in the immunoblot assay. On the basis of its molecular mass and its presence in the cytoplasmic fraction, this antigen was named p95 C. This anti-p95 C antibody was detected in six of 50 (12%) sera from patients with primary biliary cirrhosis, and in three of 31 (9.7%) sera from patients with autoimmune hepatitis, but not in any of the remaining 410 sera obtained from patients with other hepatic diseases. It is concluded that anti-p95 C antibody reacts primarily with the native form of the 95-kDa protein, and represents another possible analyte for diagnosing autoimmune liver diseases.

Persistence of gp210 and multiple nuclear dots antibodies does not correlate with recurrence of primary biliary cirrhosis 6 years after liver transplantation

Persistence of gp210 and multiple nuclear dots antibodies does not correlate with recurrence of primary biliary cirrhosis 6 years after liver transplantation

The PML and PML/RARα Domains: From Autoimmunity to Molecular Oncology and from Retinoic Acid to Arsenic

Acute promyelocytic leukemia (APL) is specifically associated to a t(15; 17) translocation which fuses a gene encoding a nuclear receptor for retinoic acid, RARα, to a previously unknown gene PML. The PML protein is localized in the nucleus on a specific domain of unknown function (PML nuclear bodies, NB) previously detected with autoimmune sera from patients with primary biliary cirrhosis (PBC). These bodies are nuclear matrix-associated and all of their identified components (PML, Sp100, and NDP52) are sharply upregulated by interferons. We show that autoantibodies against both PML and Sp100 are usually associated in sera with multiple nuclear dot anti-nuclear antibodies and demonstrate that PML is an autoantigen, not only in PBC, but also in other autoimmune diseases. In APL, the PML/RARα fusion interferes with both the retinoic acid (RA) response and PML localization on nuclear bodies, but the respective contribution of each defect to leukemogenesis is unclear. RA induces the terminal differentiation of APL blasts, yielding to complete remissions, and corrects the localization of NB antigens. Arsenic trioxide (As2O3) also induces remissions in APL, seemingly through induction of apoptosis. We show that in APL, As2O3leads to the rapid reformation of PML bodies. Thus, both agents correct the defect in NB antigen localization, stressing the role of nuclear bodies in the pathogenesis of APL.

Multiple nuclear dots antinuclear antibodies are not specific for primary biliary cirrhosis.

Multiple nuclear dots antinuclear antibodies display a specific immunofluorescence pattern on HEp-2 cells. They have been reported to be strongly associated with primary biliary cirrhosis, especially when sicca syndrome was present. To determine whether multiple nuclear dots antinuclear antibodies are specific for primary biliary cirrhosis, we studied the clinical, biochemical, immunological and morphological features of 38 patients between December 1983 and September 1990 who had serum multiple nuclear dots antinuclear antibodies detected in an immunology laboratory of a large medical center. Sufficient information was reliable in 36 patients; the group included 31 women and 5 men (mean age = 57.6 +/- 14.5, range = 30 to 87). Fifteen patients (42%) had primary biliary cirrhosis, 5 patients (14%) had type 1 autoimmune chronic active hepatitis, 4 patients (11%) had liver disease of unknown cause and 12 patients (33%) had various immunological disorders but no liver disease. Two of the patients with primary biliary cirrhosis (13%) had clinical sicca syndrome. Our study demonstrates the following: (a) serum multiple nuclear dots antinuclear antibodies are not specific for liver disease because they can be observed in one third of patients with various immunological disorders without liver involvement, and (b) serum multiple nuclear dots antinuclear antibodies are not specific for PBC because they can also be observed in type 1 autoimmune chronic active hepatitis. Our results also suggest that patent sicca syndrome is abnormally present in patients with primary biliary cirrhosis and multiple nuclear dots antinuclear antibodies.

Syndrome de Gougerot-Sjögren avec « nuclear dotset anticorps anti J01

The association of multiple nuclear dots antinuclear antibodies and anti J01 antibodies in a true Sjögren syndrome leads us to discuss about: the signification of nuclear dots, usualy associated with liver disease, and the classification of the observed Sjögren syndrome.

High Prevalence of Autoimmune Liver Disease in Patients with Multiple Nuclear Dot, Anti-Centromere, and Mitotic Spindle Antibodies

We used HEp-2 cells to compare the occurrence of multiple nuclear dot (MND), anti-centromere (ACA), and mitotic spindle antibodies (MSA) in patients with primary biliary cirrhosis (PBC) (n = 32) and primary Sjögren's syndrome (n = 50). The predictive value of these antibodies for autoimmune liver disease was evaluated among patients with chronic liver or inflammatory connective tissue diseases. MND were found in 6%, ACA in 10%, and MSA in 6% of PBC sera. Among patients with primary Sjögren's syndrome, ACA were found in one, whereas another had both MND and MSA. MND were also detected in 1 of 25 sera from patients with other chronic inflammatory connective tissue diseases. Reexamination of these three patients showed evidence of PBC in two. In a blinded study of sera from 356 patients with chronic liver diseases, MND were detected in 10 (3%), ACA in 2 (0.9%), and MSA in 4 (1.2%). All patients with MND or ACA and two of four with MSA had PBC or autoimmune chronic active hepatitis, particularly of the cholestatic type. In four of these patients the liver disease had not previously been classified. We conclude that these antibodies have low sensitivity but high predictive value for autoimmune, cholestatic liver disease.

Multiple nuclear dots antinuclear antibodies (MND-ANA) of primary biliary cirrhosis (PBC) react with 78–92KD and 96–100KD proteins of nuclear bodies

Multiple nuclear dots antinuclear antibodies (MND-ANA) of primary biliary cirrhosis (PBC) react with 78–92KD and 96–100KD proteins of nuclear bodies