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Objective: We attempted to evaluate endothelial dysfunction and the role of AECAs in systemic lupus (SL) with low disease activity. We quantified endothelial microparticles (EMps) and attempted to find the best flow cytometry method for that purpose., Methods: CD105, CD144 and CD146 were tested, individually or in combination, on EMp-enriched plasma. Twenty-three healthy blood donors and 27 SL patients were evaluated. SL patients with a SLEDAI <10 (median 2.6) were evaluated in our outpatient clinic. For each patient, EMps (CD105-CD146(+), CD45(-)) and AECAs were quantified and characterized., Results: The monochrome composite marker CD105-CD146 appeared to be the most efficient in detecting EMps. SL patients had more circulating EMps than healthy donors: respective median values were 2575 and 130 EMps/microl (P < 0.001). SL patients had more CD54(+) and CD54(-) EMps than healthy donors (496 vs 34 EMps CD54(+)/microl, P < 0.0001; 1875 vs 89 EMps CD54(-)/microl, P < 0.0001). The ratio CD54(+) EMps/total EMps was lower for lupus patients than for healthy individuals (20.3 vs 33.7%, P = 0.03). Twenty-four patients (89%) were positive for AECAs. EMp counts were not significantly higher for patients with AECAs., Conclusion: Monochrome composite marker is efficient in detecting the whole population of EMps using flow cytometry. SL patients with low disease activity have a marked endothelial dysfunction. EMps released from the endothelium originate from activated and non-activated cells. AECAs do not seem to be the main cause of endothelial dysfunction in this population.

In primary biliary cirrhosis (PBC) serum markers other than anti-mitochondrial antibodies (AMA) are promising in terms of disease severity and comorbidities, as well represented by anti-nuclear antibodies (ANA). The aim of the present study was thus to evaluate the prevalence and clinical significance of a large profile of serum autoantibodies in PBC sera. We utilized 69 sera from European patients with PBC (including 20 AMA-negative) and 297 sera from geographically and sex-matched healthy controls. All sera were tested for the presence of ANA and autoantibodies associated with thrombophilia, vasculitis, and gastrointestinal disease. Autoantibodies other than AMA were detected in 53/69 (76%) PBC sera vs. 105/297 (35%) among controls. The prevalence of ANA (targeting dsDNA, Sm, chromatin, ribosomal-P, RNP, SmRNP, SSA, SSB, and centromere) and thrombophilia-associated autoantibodies (i.e. anti-beta2GPI, phosphatydilserine, prothrombin) was common among patients with PBC. When clinical features were compared, the presence of anti-prothrombin IgM was associated with a worse prognosis as represented by a higher Mayo score. We demonstrate an increased prevalence of ANA and thrombophilia-associated autoantibodies in PBC sera and an association between the latter autoantibodies and PBC stage. The role of thrombophilia-associated antibodies will warrant further studies, based in particular on the incidence of portal hypertension at early stages of PBC., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Recently, we have observed that the association of anti-F-actin autoantibodies (Abs) with anti-alpha-actinin Abs (double reactivity) was correlated with liver disease activity in autoimmune hepatitis type 1 (AIH-1; Guéguen et al., J Clin Immunol 26:495-505, 2006). As anti-alpha-actinin Abs are also associated with anti-single-stranded (ss) DNA in 16 of 50 (32%) AIH-1 patients, compared with 16 of 401 (4.0%) liver disease control patients, we sought to characterize these Abs in AIH-1. When associated, anti-ssDNA Abs cross-react with anti-alpha-actinin Abs, but neither with anti-double-stranded DNA Abs nor with anti-F-actin Abs. Furthermore, anti-alpha-actinin Abs are associated with high-avidity anti-ssDNA Abs in AIH-1. In addition, double reactivity against alpha-actinin and ssDNA was correlated with clinical and histological activity of the disease and untreated AIH-1 patients.

Objective: Anti-double-stranded DNA (anti-dsDNA) antibodies may contribute to the pathogenesis of glomerulonephritis (GN) by cross-reacting with alpha-actinin in murine models and in some patients with systemic lupus erythematosus (SLE). We therefore sought to determine possible disease associations with serologic and clinical features and to characterize this new autoantibody specificity., Methods: One hundred patients with SLE were recruited into this multicenter study, as well as 100 rheumatic disease controls and 2,100 healthy blood donors. Clinical disease was evaluated by the SLE Disease Activity Index (SLEDAI; excluding the anti-DNA component). Anti-dsDNA antibodies were detected by conventional enzyme-linked immunosorbent assay (ELISA) and by a commercial enzyme immunoassay (EIA). Anti-alpha-actinin antibodies were detected by ELISA, and their specificity was confirmed by Western blotting and by indirect immunofluorescence using rat kidney sections and mesangial cells as substrates. Highly positive sera were selected for absorption experiments and were affinity-purified for cross-reactivity studies and measurement of antibody avidity., Results: Sera from 62 of the SLE patients had anti-dsDNA antibodies; 21 of these sera also had anti-alpha-actinin antibodies, as compared with 1 of the 38 sera without anti-dsDNA antibodies. Of the 22 patients with anti-alpha-actinin antibodies, 10 had GN, as compared with 14 of the 78 without anti-alpha-actinin antibodies (P < 0.01). In patients with GN, anti-alpha-actinin, but not anti-dsDNA, antibodies correlated with the SLEDAI score (minus the anti-DNA component) and with treatment. The fraction of serum anti-dsDNA antibodies that cross-reacted with alpha-actinin exhibited high avidity for dsDNA, as determined using a commercial EIA for high-avidity anti-dsDNA antibodies and an in-house conventional ELISA., Conclusion: The alpha-actinin-binding antibodies are significantly associated with GN in SLE. Whether such autoantibodies may anticipate the development of this complication of SLE remains to be verified.

Systemic lupus erythematosus is associated with a plethora of immunological abnormalities. First, there are antinuclear autoantibodies directed towards insoluble (mainly desoxyribonucleic acid, histones and nucleosomes) or soluble nuclear components (mainly Sm, RNP and Ro/SSA particles). There are then autoantibodies other than antinuclear, recognizing cells (erythrocytes, lymphocytes, neutrophils, endothelial cells), organelles (Golgi apparatus, ribosomes) or molecules (cardiolipids, C1q, stress proteins). Finally, there are immunological abnormalities other than autoantibodies, such as immune complexes, monoclonal immunoglobulins or complement variations. In fact the pathogenetic role of these perturbations remains a matter for speculation.

The possible association between the presence of antiperinuclear factor (APF) and clinical and genetic parameters was investigated in 54 Israeli patients with rheumatoid arthritis (RA). Rheumatoid factor (RF) was detected in the sera of 43 patients (80%) and APF was positive in 33 (61%). No significant statistical differences were found in the presence of HLA-DR4 and/or DR1 between APF-positive and -negative patients. Furthermore, neither the Ritchie articular index nor the patient's functional class correlated with the presence of APF. The results of our study suggested that although Israeli patients have a different genetic background, the presence and behaviour of APF is similar to that of other Caucasian populations.

Our objective was to study the interaction between major histocompatibility complex (MHC) class II and T-cell receptor (TCR) alleles in the recognition of extractable nuclear antigen-derived peptides in 32 patients with systemic lupus erythematosus and 173 of their family members. MHC genes were analyzed using sequence specific oligonucleotides, and TCR beta-chain gene polymorphism using restriction fragment-length polymorphism. One dominant peptide (as defined by enzyme-linked immunosorbent assay autoantibody reactivity) was identified in each antigen studied: peptide 1-20 in Sm-D, peptide 35-58 in U1-RNP-A, and peptide 304-324 in the Ro/SSA 60 Kd protein. None of the MHC class II and TCR beta haplotypes was directly associated with any of the autoantibodies. Twenty-six subjects had antibodies to the peptide Sm-D1-20; nine of them were DRB1*0101/DQB1*0501. Among subjects with this haplotype, the number of responders was higher (p < 0.028, p corrected, pc = 0.336) in those with the 2-25-9 TCR beta haplotype than in the remainder. Conversely, the number of DRB1*04/DQB1*0302 responders was lower (p < 0.030, pc = 0.360) among subjects with the 23-20-9 TCR beta haplotype than in those without. The odds ratios (OR) were 4.23 and 0.21, respectively. Of the 54 subjects positive for anti-U1-RNP-A 35-38, 13 were DRB1*0101/DQB1*0501 and eight DRB1*04/DQB1*0302. The percentage of responders was higher (p < 0.041, pc = 0.492, OR = 3.48) in the former group of subjects with the 2-25-9 TCR beta haplotype, and lower (p < 0.02, pc = 0.024, OR = 0.09) in the latter with the 23-20-9 TCR beta haplotype. Three of the 12 anti Ro/SSA 60Kd 304-324-positive subjects were DRB1*0101/DQB1*0501. All had the 2-25-9 TCR beta haplotype (p < 0.046, pc = 0.552, OR = 6.29) and none the 23-20-9 (p < 0.031, pc = 0.372, OR = 0.10). The same combinations of genes were associated with high/low response toward the three peptides. These data provide evidence for an interplay of the MHC class II and TCR beta alleles in the control of specific autoantibody response to well-defined nuclear Ag peptides.

The aim of the present study was to evaluate the prevalence of antiperinuclear factor (APF) in patients with spondylarthropathy and the relationships between this autoantibody and a variety of clinical, radiological and serological findings. We conducted a retrospective review of the medical records of all patients first admitted to the Rheumatology Unit of the Brest University Medical School Hospital from 1 January 1986 to 31 December 1994, and who met the European Spondylarthropathy Study Group (ESSG) criteria at admission. Each patient had a standard battery of tests. Serum samples from 123 of 126 patients suffering from spondylarthropathy were examined for the presence of APF. Thirty-three patients (26.8%) had APF at a titre > or = 1/80. There were no significant relationships between various demographic, clinical or radiological characteristics and the presence of APF. However, the subgroup of APF-positive patients had a higher prevalence of both rheumatoid factors (RF), although not significant, and antikeratin antibody-positive serum than the rest. These results suggest that some patients had rheumatoid arthritis (RA) and three patients with APF > 1/100 and who were RF positive met ACR criteria for RA. APF should thus be used only as an additional serological marker in cases where clinical features suggest the association of spondylarthropathy with RA.

Antiperinuclear factor (APF) and antikeratin antibody (AKA) have long been known to be associated with rheumatoid arthritis. Human buccal mucosa epithelial cells have hitherto been required as the substrate in the APF test, while AKAs are detected on rat esophagus sections, using an indirect immunofluorescence technique. These two autoantibodies proved to be interrelated. Cytoplasmic inclusions in buccal cells have presumptively been termed keratohyalin granules and the APF target antigen colocalizes exactly with that of antiprofilaggrin antibody within the perinuclear organelles. The latter protein has convincingly been identified as the genuine specificity of the so-called AKA.

Although antiperinuclear factor (APF) has the same specificity for rheumatoid arthritis (RA) as rheumatoid factor (RF), there is no evidence that this specificity is maintained in patients with positive RF-agglutination tests. Thus, we evaluated the specificity and usefulness of APF for RA diagnosis, regardless of RF titre. APF was tested (1:100 threshold) on 214 sera sent for RF evaluation over a 9-month period. These sera were previously determined to have latex or Rose-Waaler (RW) titres > or = 12 or 4 IU, respectively, but not necessarily above the threshold values of 100 and 32 IU. The APF test was performed blindly, and physicians were not advised of the results. In the patient population (119 RA and 95 non-RA) APF still demonstrated good specificity (0.82) for RA. As expected, APF proved useful for RA diagnosis in 28/33 (85%) RA cases with an RF level below 1:100 for latex and 1:32 for RW, thus reducing the number of 'seronegative' RA from 33/119 to 5/119. However, it also improved the serological positive predictive value for RA, even in cases when RW results were > or = 32 IU. Indeed, the positive predictive value for RA when both tests were positive was 0.94 (68/72), whereas concordant results (either positive or negative) for both APF and RW tests allowed correct classification (RA or non-RA) in 94% of cases.

BEG-2 is a monoclonal antibody produced by the human-human hybridoma technique from a 12 weeks old human fetus. A polyclonal antiserum was raised in an (NZW x Half-lop hybrid) rabbit against BEG-2 and the anti-BEG-2 anti-idiotype was purified and characterised. Using this rabbit reagent the expression of the BEG-2 beta idiotype was analysed in 12 patients with active rheumatoid arthritis and their close family members (n = 54). Twenty five sera from healthy controls were analysed to establish a normal range. Ten of 12 patients (83%) with rheumatoid arthritis expressed the BEG-2 idiotype as well as 11 of 54 healthy unaffected relatives (20%).

To evaluate the usefulness for the diagnosis of rheumatoid arthritis of tests for rheumatoid factors, antiperinuclear factors, antikeratin antibodies, and the HLA DR4 antigen, we retrospectively reviewed the medical records of 138 patients consecutively admitted to our rheumatology department between January 1, 1988 and December 31, 1990 for evaluation of peripheral inflammatory joint manifestations. Each patient had a standard work-up including a physical examination, laboratory tests, and roentgenograms. In 1994, after a follow-up of three to six years, the final diagnosis was rheumatoid arthritis in 39 patients and another well-defined disorder in 63; no diagnosis was established in 36 patients, among whom nine were lost to follow-up. The decreasing order of diagnostic usefulness was antiperinuclear factors, HLA DR4, rheumatoid factors (latex test), and antikeratin antibody. The likelihood of rheumatoid arthritis was greatest in those patients with positivity of two of the three following markers: rheumatoid factors, antiperinuclear factors, and the HLA DR4 antigen.

Objective: For rheumatoid arthritis (RA), antiperinuclear factor (APF) is as efficient a marker as rheumatoid factor (RF). However, the prevalence and significance of APF of the IgA isotype in active RA, as well as its correlation with RF-IgA, have not been determined. Our goal was to obtain information on these points., Methods: APF-IgA were screened in 80 sera from patients with active RA, prospectively and consecutively selected over an 8-month period. Sera from 22 patients with Sjögren's syndrome and 50 with lupus were also studied retrospectively for APF-IgG and IgA., Results: APF-IgA were found at a 1:10 dilution or above in 31 RA sera (39%), which were all positive for APF-IgG as well at higher titers. In the 64 sera positive for APF no correlations were found between APF-IgA and IgA or immune complexes-IgA, latex, the Rose-Waaler test and RF-IgA. Conversely, an association of APF-IgA was found with both APF-IgG (p < 0.0001) and anti-stratum corneum of rat esophagus (ASC)-IgG (p < 0.0001). APF-IgA, though correlated with the presence of secondary sicca syndrome in RA (p = 0.0023), was not more frequent (5/22) in primary Sjögren's sera., Conclusions: RF-IgA and APF-IgA are not correlated. Despite its localization in the mucosae, the target antigen for APF elicit fewer IgA antibodies in RA than does the RF target.

Our purpose was to evaluate the role of Epstein-Barr virus (EBV) in the production of antiperinuclear factor (APF), a rheumatoid arthritis (RA)-specific marker, and the autoimmunogenicity of 'perinuclear antigens' (PNA) found within the buccal mucosa epithelial cells used as a substrate in the APF assay. Fifty APF-positive and 50 APF-negative sera from RA patients were examined for the presence of antibodies to six different EBV antigens. APF was tested in the serum of 40 patients with acute infectious mononucleosis (IM), 48 PNA-expressing donors and 29 non-PNA-expressing donors. The EBV genome was sought in the saliva and buccal cells of both types of donors. The targeted granules of cells from a PNA-expressing donor were studied by electron-microscopy. The prevalence of anti-EBV antibodies was similar in RA patients with and without APF, whereas the APF-positive sera was elevated in acute IM. The titres of anti-EBV antibodies did not correlate to the expression of PNA in the buccal cells of the donors. There was no relationship between this expression and the presence of the EBV genome in the material obtained from 'positive' donors, relative to 'negative' donors. No virus-like particles could be detected inside the granules by electron microscopy. These results indicate that there are no direct relationships between EBV and the APF/PNA system, although APF was present in a number of patients with IM.

We describe a human monoclonal antibody designated WRI 176 beta and a common idiotype that it carries. This antibody was derived from the spleen of a patient with SLE. WRI 176 is an IgM kappa monoclonal reacting with ssDNA, dsDNA, poly(dT) and it is likely that mAb WRI 176 beta is a representative of the so-called natural autoantibodies. The common Id designated WRI 176 Id beta is located on the heavy chain of the mAb WRI 176 beta molecule and appears to be located outside the binding site. Sequence analysis of the WRI 176 beta heavy chain showed it to be highly homologous (97.3%) with a germline gene 56PI derived from a human fetus. In a retrospective analysis, although 44% of SLE patients had raised levels of the WRI 176 beta no correlation was found with the activity of the disease. The idiotype was also expressed frequently in a range of autoimmune rheumatic and infectious diseases and in some healthy first-degree relatives of SLE patients.

This study aims to describe a novel antinuclear antibody directed to proteins only accessible during the mitosis: anti-"dividing cell antigen" (DCA) antibody. A total of 709 disease-associated and control sera was tested by indirect immunofluorescence using a variety of cell lines as substrate. Cells were treated with enzymes and antibodies absorbed with nuclear antigens. Antibodies to DNA, histone subfractions, and synthetic peptides were evaluated using enzyme-linked immunosorbent assays. Cell extracts were electrophoresed before and after synchronization and sera tested on the blots. The anti-DCA antibody was demonstrated in 10 of 183 SLE patients but virtually never in other connective tissue diseases. The DCA was sensitive to HCl and proteolytic enzymes and the anti-DCA binding inhibited by histones H2A and H2B. Differences of anti-H2A and anti-H2B were observed between anti-DCA antibody-positive and anti-DCA antibody-negative sera, and antibodies specific for the 1-15 region of H2A, the 1-25 region of H2B and the 1-29 region of H4 were more frequent in the former sera than in the latter. The anti-DCA antibody was shown to react with a 60-kDa protein. Our findings suggest that the anti-DCA antibody is directed to a protein complex containing H2A and H2B.

We have developed isotype-specific enzyme-linked immunosorbent assays to assess anti-Ro/SSA and anti-La/SSB IgG subclasses in 31 patients with primary Sjögren's syndrome. The anti-Ro/SSA antibody production was largely but not totally restricted to IgG1, whilst the anti-La/SSB subclass distribution varied from one patient to another. IgG2 and IgG3 anti-La/SSB was more frequent in those patients with extraglandular manifestations. In addition, there were more increases in the IgG2 and IgG4 contribution to anti-La/SSB activity in the 16 DR3-positive patients than in the remaining 10.

The antiperinuclear factor (APF) test is as sensitive and specific for rheumatoid arthritis as the classical rheumatoid factor tests. Five European laboratories decided to perform a consensus study on the interlaboratory variability of the APF test. They used different donor cells, different conjugates and different criteria for positivity. However, the results differed by not more than one two-fold dilution step, when expressed in international units using WHO reference rheumatoid arthritis serum as the standard.

Antiperinuclear factors (APF) are directed to epithelial cell "kerato-hyaline granules". Standardization of the APF test has been achieved, but the way to express the results is still debatable. APF were found to be present in 76% of rheumatoid arthritis (RA) patients: thus the sensitivity and the specificity for RA were 76 and 97%, respectively. No clinical or serological associations were substantiated in RA. The antigens targetted by these auto-antibodies are extremely variable from one to another donor.

Five synthetic peptides corresponding to the N-, the C- and a central domain in 60-kD SSA/Ro protein were prepared and tested with sera from 112 patients with systemic lupus erythematosus (SLE), 55 with primary Sjögren's syndrome (pSS) and 29 with rheumatoid arthritis. Among these five fragments, one representing residues 21-41, was recognized by antibodies in 57% of pSS patients. Interestingly, this peptide was recognized by only a few (less than or equal to 7%) of SLE sera, while 63% of pSS sera and 46% of SLE sera tested in parallel possessed antibodies reacting in ELISA with purified 60-kD SSA protein. The ELISA results were compared with the pattern of reactivity obtained in immunodiffusion and immunoblotting. The results indicate that the sensitivity of ELISA using peptide 21-41 and pSS sera was in the same range as immunoblotting and higher than immunodiffusion. Thus the peptide 21-41 proved useful for the detection of anti-SSA antibodies in the sera of patients with pSS. Furthermore, a positive ELISA using peptide 21-41 could be of potential use to discriminate pSS with systemic features from SLE. The fact that peptide 21-41 is recognized by antibodies in pSS but only by very few SLE sera implies that different mechanisms are involved in the anti-SSA immune response in these two autoimmune diseases.

The antiperinuclear factor (APF) test raises two main problems: the unpredictability of the cells used as substrate and the difficulty in expressing the results. We propose that 10% of the cells have to be stained by a given serum in order for it to be considered positive. APF were found to be present in 76% of rheumatoid arthritis (RA) patients, 3% of healthy controls and occasionally in disease controls. The production of APF was significantly (p less than 0.01) related to the presence of rheumatoid factor in RA, and IgG antibody was predominant in the APF test.

Since the antiperinuclear factor (APF) test on human buccal cells is rather unpredictable, we have investigated the possible factors determining the expression of appropriate antigens by the cells. We failed to find any relationship of the expression of perinuclear antigens to the donor's smoking habits, the degree of contamination with saprophytic bacteria, the presence or absence of blood group substances in saliva, or the titers of serum antibodies to Epstein-Barr virus. Family studies were also performed to further elucidate a genetic predisposition to the expression of the APF antigen.

Cord blood B cells were immortalized in vitro with Epstein-Barr virus (EBV). Supernatants containing greater than 500 ng/ml IgM from clones/lines were tested for expression of anti-DNA-associated 16/6 and PR4 idiotypes (id) by ELISA. Four of 70 lines, but no clones, were positive for 16/6 id and none expressed the PR4 id. The presence of 16/6 id on four cell lines was associated with specificity for ssDNA, cardiolipin and Fc of IgG. No association was seen with binding to the K30 polysaccharide of Klebsiella. One clone binding this antigen also had anti-ssDNA, anti-Fc and anti-cardiolipin activity but did not express 16/6 id. Our data support the germ-line nature of the 16/6 id and are consistent with the notion that IgM autoantibody-producing B cells use VH genes which are part of the normal B cell repertoire.

Anti-perinuclear factors (APF), IgM-, IgG- and IgA-rheumatoid factors have been detected in six, five, one and three out of 20 patients with primary myxoedema, respectively. We were unable to find APF in 22 patients with Hashimoto's thyroiditis nor in 20 patients with Graves' thyrotoxicosis. APF appears to be a marker for non-organ specific autoimmune diseases.

Seronegative systemic lupus erythematosus is defined as a SLE devoided of antinuclear factors as well as of LE cells when at least 4 out of the 14 ARA criteria are present. We describe herein two case reports and review previous literature concerning this topic. This kind of SLE is characterized by a high incidence of Raynaud's disease, photosensitivity, oral ulcerations, alopecia and perhaps less frequent kidney and central nervous system involvement. The hypotheses about the absence of ANF are discussed. The awareness of such a SLE ("devoided of ANF rather than" seronegative") is to be kept in mind from a chemical, therapeutic and pathophysiologic point of view.

The results of routine antihistone antibody (AHA) assay in a preliminary series of 189 sera are presented. There were 23 positive tests (systemic lupus erythematosus, 8 cases; drug induced SLE, 4 cases; rheumatoid arthritis 7 cases; and multiple sclerosis, 1 case; chronic active hepatitis, 1 case; systemic sclerosis, 1 case and primary biliary cirrhosis 1 case). The results of routine assay in 5 other patients groups are reported: 30 spontaneous SLE (9 positive AHA), 63 rheumatoid arthritis (2 positive AHA), 19 Sjögren syndrome (no AHA), 11 primary biliary cirrhosis (1 positive AHA) and 7 mixed connective tissue disease (no AHA).

Antibodies directed against double-stranded (native) desoxyribonucleic acid (dsDNA) were detected by the immunofluorescence technique on Crithidia luciliae in 38 out of 58 patients with systemic lupus erythematosus (SLE) and in 22 out of 296 controls with autoimmune diseases. The SLE patients had high titers of anti-dsDNA antibodies which belonged at least to the IgG class and fixed the complement in 20 out of 38 cases. These complement-fixing antibodies differed from the others in their greater activity, as evaluated by C3 levels, and in their association with a high incidence of renal lesions.

Tests for antivimentin antibodies (AVA) were performed on 50 systemic lupus erythematosus (SLE) and 63 control sera by indirect immunofluorescence and enzyme linked immunosorbent assay (ELISA). The prevalence was significantly raised in SLE (38% and 50% of sera positive for IgM-AVA and IgG-AVA, respectively, by immunofluorescence; 36% and 64% of sera positive for IgM-AVA and IgG-AVA, respectively, by ELISA) in comparison with the control sera. A significant correlation existed between IgM-AVA, on the one hand, and anticardiolipin antibodies (ACA) and anti-single-stranded DNA (ssDNA), on the other. A stepwise principal component analysis demonstrated that IgM-AVA and IgG-AVA accounted for 71% of the total variance in SLE (50 patients x 5 parameters = total variance). Twenty ACA positive serum samples from patients with syphilis were therefore tested for the presence of AVA, but hardly any were found to be positive. IgM-AVA from patients with SLE were inhibited by cardiolipin and absorbed with ssDNA. An association between AVA positivity and arthralgia was also shown in SLE.

Antiperinuclear factor (APF) and IgG-rheumatoid factor (IgG-RF) has been found in 64% and 48% of cases of rheumatoid arthritis, 36% and 50% of cases of psoriasis and 31% and 45% of cases of primary Sjögren's syndrome. A close relationship between APF and IgG-RF is suggested by statistical and experimental data. Purified IgG-RF has some degree of APF activity.

Forty-seven patients were diagnosed as having systemic lupus erythematosus (SLE) and 34 patients primary Sjögren's syndrome (SS); 30 controls were also studied. Anti cardiolipin (CL), anti double-stranded DNA (ds DNA) and anti single-stranded DNA (ss DNA) antibodies were determined by the enzyme-linked immunosorbent assay. Elevated anti-CL antibody levels were detected in 47.8 p. 100 (n = 46) of patients with SLE and in 85.3 p. 100 (n = 34) of patients with SS, but only once in controls. Elevated ss DNA were detected in 91.5 p. 100 (n = 47) of patients with SLE and in 18.3 p. 100 of patients with SS but never in controls. Elevated anti-ss DNA were detected in 93.3 p. 100 and 97.1 p. 100 respectively of patients with SLE and SS and in 3.3 p. 100 of controls. There was no correlation between anti-CL and thrombosis, circulating lupus anti coagulant or VDRL. The most striking association, however, was between anti-CL and anti ss-DNA antibodies in SLE. There was no correlation between anti-CL and anti ds-DNA antibodies in SLE patients. Anti CL antibodies were correlated both to ss-DNA and anti ds-DNA in SS patients. Absorption of positive anti-CL antibodies sera were done on DNA (ss-DNA and ds-DNA) affinity column chromatography: anti-CL antibodies were absorbed only by ss DNA in SLE and by both ss DNA and ds DNA in SS.

Anti-perinuclear antibodies (APN) were studied in 547 subjects, 123 of whom suffered from rheumatoid polyarthritis (RP). They were detected 88 times in the latter group (72 percent). 26 percent of RP were without serological abnormalities when only rheumatoid factors were considered (latex, Waaler-Rose, Waaler-Rose LOR, rheumatoid factors by indirect immunofluorescence). The rate dropped to 10 percent when APN were included. This test is therefore sensitive. It is also specific as APN exists in only 11 percent of non-rheumatoid rheumatological diseases not including psoriasis (42 percent) and in 16 percent of other auto-immune diseases. In addition, there is a correlation (p less than 0.01) between APN level and the evolution of the rheumatoid illness. APN appears early in an illness and is thus of diagnostic and prognostic interest in RP.

Antiperinuclear factor (APF) was detected in 7 out of 38 patients with autoimmune liver disease (AILD) and in 7 out of 83 patients with non-autoimmune liver disease (NAILD). Anti-keratin antibodies were found in 2 out of 18 patients with AILD and in 3 out of 32 patients with NAILD. Neither APF nor antikeratin antibody was significantly more frequent in AILD than in NAILD. The incidence of APF was shown to be greater (p less than 0.02) in patients with rheumatoid factor (RF) and/or antinuclear antibody. This supports the hypothesis that APF is connected with RF rather than with rheumatoid arthritis, although the presence of APF is evidence towards the diagnosis of rheumatoid arthritis.

Neonatal lupus syndrome can be considered as being associated with pregnancy in women with lupus. Two antinomic cases are reported: a pregnancy in a woman presenting with Sjögren's syndrome, bearing a child with neonatal lupus syndrome (atrioventricular block and antinuclear antibodies) and a pregnancy in a woman presenting with lupus and giving birth to a normal child with antinuclear antibodies. These 2 case reports allow us to speculate on the pathophysiology of neonatal lupus syndromes in which the type of antinuclear antibodies seems to play a major role.

Antiperinuclear factor (APF) might be a specific serum rheumatoid factor directed towards keratohyaline granules. It was found to be present in 40 of 79 (50.6%) patients with primary and in 21 of 36 (58.3%) patients with metastatic lung cancer, compared with 12 of 95 (12.6%) sex- and age-matched normal controls. Additionally, APF frequency and titer correlated well with tumor dissemination, even though no relationship could be shown with histopathological type.

Serum from 91 patients with Sjögren's syndrome (SS) was examined for antiperinuclear factor (APF). Nine out of 29 patients with SS alone (31.0%) were positive as opposed to 27 out of 40 with SS + rheumatoid arthritis (67.5%) and to 3 out of 22 with SS + other autoimmune disorders (13.6%). A clear relationship was established between APF and agglutinating or non-agglutinating rheumatoid factor.

Antiperinuclear factors (APF), studied in 90 patients suffering from psoriasis, were found in psoriasis without arthritis, in psoriasis with psoriatic arthritis and in psoriasis with true rheumatoid arthritis (RA): respectively 57, 36 and 43 p. 100. Patients with APF did not differ from patients without APF apart form rheumatoid factors detected by indirect immunofluorescence. They were much more frequent in psoriasis with APF. These results are compared with those of RA. They lead to look for other auto-antibodies in psoriasis.

A broad range of autoreactivity among a group of 12 French patients with rheumatoid arthritis (RA) and 58 of their healthy first degree relatives has been identified. Over 15% of the patients were found to have antibodies to ssDNA, histone H1, H2A, and H2bB. Among the relatives, IgG and IgM rheumatoid factor and antibodies to ssDNA, H2A, and H4 were present in more than 10%. Even more remarkable, a common anti-DNA antibody idiotype designated PR4, known to be present in 70% of patients with systemic lupus erythematosus (SLE), was found in approximately 30% of both patients with RA and their healthy relatives. This is quite different from its lack of increased expression in relatives of patients with SLE and suggests that in the family members of those with RA a particular combination of environmental influence on germline gene expression is responsible.