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We read with great interest the multicentre study of Damoiseaux et al 1–3 on the detection of antineutrophil cytoplasmic antibodies (ANCA). ANCAs are important laboratory markers to support the diagnosis of ANCA-associated small vessel vasculitis (AAV), including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Traditionally, laboratories screen for ANCA by indirect immunofluorescence (IIF) and IIF positive samples are further evaluated for antibodies to proteinase 3 (PR3) or myeloperoxidase (MPO) by specific immunoassays. Such diagnostic algorithm is based on an international consensus statement on ANCA testing issued in 1999.4 Over the last two decades, the diagnostic performance of immunoassays has significantly improved. The recent multicentre study showed a …

International audience; Anti-signal recognition particle (SRP) antibodies are important serological markers for the diagnosis and the prognosis of idiopathic inflammatory myopathy (IIM), especially to distinguish immune-mediated necrotizing myopathy (IMNM). This study was set up to investigate the phenotype associated with anti-SRP antibodies and to evaluate the methods for detecting these antibodies. Clinical and biological data were retrospectively obtained from 60 adult patients with anti-SRP antibodies detected by a dot immunoassay from 12 centers. Thirty-six (60 %) out of these 60 patients suffered from an IIM, and among them, 21 patients were diagnosed as IMNM. Among patients with a definite IIM, proximal weakness and myalgia were prominent symptoms at the time of diagnosis. Only few patients displayed severe extra-muscular symptoms such as cardiac involvement or severe myositis. Mean creatine kinase levels were high for all patients except for two of them. When testing by indirect immunofluorescence (IIF) on HEp2 cells, the fraction of patients displaying the typical anti-SRP fine speckled staining of the cytoplasm was higher in patients with IIM (30/36) (83 %) than in patients with non-IIM (3/24) (12.5 %) (p

New treatment strategies require that rheumatoid arthritis (RA) be diagnosed as early as possible. New diagnostic markers were required, because rheumatoid factors (RF), until now criteria for classification of RA, are not sufficiently specific and sometimes appear late, thereby limiting their diagnostic usefulness. The objective of this review is to describe the current state of knowledge and more particularly to analyze the interest of new RA autoanti-bodies, called anti-peptide or anti-citrullinated protein anti-bodies (ACPA). Other autoanti-bodies have been described, including anti-Sa, anti-alpha enolase, and anti-calpastatin autoanti-bodies. Nonetheless, their diagnostic value remains limited compared to ACPA. Accordingly, in daily practice today, the only autoanti-bodies that must be tested for to diagnose RA are the ACPAs and RFs. The discovery of ACPA (initially called anti-keratin and anti-perinuclear anti-bodies) was a major step forward for the laboratory diagnosis of RA. The tests most often used routinely areenzyme-linked immunosorbent assays(ELISA) with cyclic citrullinated peptides, whence the name anti-CCP autoanti-bodies. Accordingly, the two terms ACPA and anti-CCP can both be used. The diagnostic value, in particular their specificity, is on the order of 95%, regardless of the method of identification. These markers are very useful and are often present earlier than RF. These ACPA also have prognostic value because they are associated with more aggressive forms of RA. On the other hand, their value over time, in particular, their fluctuation as a function of treatment, is more controversial. In practice, it is recommended to test for both RF and ACPA in a diagnostic work-up for early RA. During follow-up, the value of testing for these autoanti-bodies has not been demonstrated, but additional studies are still necessary with the anti-CCP autoanti-bodies and the new anti-citrullinated protein autoanti-bodies.

Our objective was to evaluate the prevalence of autoantibodies to cyclic citrullinated peptides (anti-CCP aAbs) in a cohort of patients with a variety of inflammatory or non-inflammatory rheumatic diseases other than rheumatoid arthritis (RA). Six hundred and nine serum samples were tested for anti-CCP aAbs and for rheumatoid factor (RF) using enzyme-linked immunosorbent assays and immunonephelometry. The prevalence of anti-CCP aAbs and RF reached 10% and 25%, respectively, using the positive cutoff value suggested by the manufacturers. Using a higher cutoff value (50 U/ml) for both aAbs, the prevalence was lower with 6% and 16%, respectively. The specificity of both markers for RA thus reached 94% and 84%, respectively. Anti-CCP aAbs were found to be elevated in inflammatory and also in non-inflammatory rheumatic diseases in the same proportion. Clinical data obtained for 36 positive patients showed that 17% developed RA within 5 years. In conclusion, anti-CCP aAbs are clearly more specific than RF for RA. Follow-up of anti-CCP aAbs-positive patients with inflammatory or non-inflammatory rheumatic diseases other than RA could be important considering the predictive value of these aAbs for the development of RA.

We report three patients with anti-signal recognition particle antibodies who had different presenting clinical pictures, mimicking acute polymyositis, limb-girdle muscular dystrophy, and acute rhabdomyolysis. Muscle biopsies typically showed necrotizing myopathy with little or no inflammation and deposits of membrane attack complex (C5b-9) in endomysial capillaries. The clinical course was severe in two patients and mild in one. The combination of corticosteroid with either an immunosuppressive agent or intravenous immunoglobulins was required to improve the condition of these patients.

The usefulness of immumoglobulin (Ig) A antibodies to gliadin (AGA-IgA) in addition to IgA anti-endomysium and tissue transglutaminase antibodies was evaluated in 4122 children younger than 2 years with a suspicion of coeliac disease (CD). Eight percent (312/4122) displayed IgA anti-endomysium and/or IgA anti-tissue transglutaminase, whereas 2.1% (85/4122) displayed only AGA-IgA. Clinical data were obtained for 62 of 85 children with isolated AGA-IgA, and 33 children underwent a duodenal biopsy. Histologically proven CD was established for 5 patients, whereas 57 children were diagnosed to experience other diseases. The systematic detection of AGA-IgA using native gliadin conferred no additional diagnostic benefit for the diagnosis of CD in children younger than 2 years of age, except for rare cases.

Objective To identify immunodominant epitopes in natural filaggrin that are reactive with antifilaggrin autoantibodies (AFA) in the sera of patients with rheumatoid arthritis (RA) and to explore their use in a diagnostic assay format. Methods Based on the results of epitope mapping of human natural filaggrin as well as molecular modeling and computational chemistry, synthetic peptides together with recombinant citrullinated filaggrin were evaluated by a line immunoassay (LIA) for AFA detection. Diagnostic performance was assessed using 336 RA and 253 disease control sera and was compared with that of reference methods. Results Several immunoreactive epitopes were identified in natural filaggrin, all of which contained at least 1 citrulline residue. Three antigenic substrates, including 2 synthetic peptides and recombinant citrullinated filaggrin showing maximal reactivity on LIA, were finally selected. Using the 3-antigen LIA3, overall sensitivity, specificity, and positive predictive value for RA were 65.2%, 98.0%, and 89.1%, respectively, compared with 61.9%, 98.8%, and 92.8% using the 2-antigen LIA2 (without recombinant protein). Thirty-seven percent of the rheumatoid factor (RF)-negative RA samples (30 of 81) were AFA-positive by LIA2, and 52 of 54 RF-positive control samples had no AFA detected on LIA2. Higher specificity and sensitivity were obtained by LIA2 versus anti-RA33 immunoblot, whereas good agreement was observed with antikeratin antibody testing. LIA performed significantly better than AFA immunoblotting using natural filaggrin, at a specificity level of 99% (P = 0.0047). Conclusion Citrullinated residues are present in immunoreactive epitopes of natural human filaggrin. AFA can be readily detected by citrullinated peptides in an LIA-based test, resulting in high specificity and positive predictive value for RA. The LIA could serve as a user-friendly alternative to existing immunofluorescence tests and AFA immunoblot techniques. Given its complementarity to RF, this test can be a valuable tool in the differential diagnosis of arthritis.

Autoantibodies to nuclear antigens, i.e. antinuclear antibodies (ANA), antibodies to double-stranded DNA (dsDNA) and extractable nuclear antigens (ENA), are useful as diagnostic markers for a variety of autoimmune diseases. In March 2010, the Belgian national External Quality Assessment Scheme sent a questionnaire on ANA, anti-dsDNA and anti-ENA antibody testing designed by the Dutch EASI (European Autoimmunity Standardization Initiative) team, to all clinical laboratories performing ANA testing. Virtually all laboratories completed the questionnaire (97·7%, 127/130). This paper discusses the results of this questionnaire and provides valuable information on the state-of-the-art of ANA, anti-dsDNA and anti-ENA antibody testing as practiced in the Belgian laboratories. In addition, this work presents practical recommendations developed by the members of the advisory board of the scheme as a result of the outcome of this study.

L’immunofluorescence sur cellules HEp2 demeure la technique de choix pour la recherche des anticorps anti-cytoplasmiques specifiques de la polymyosite. De nombreux reactifs ont ete developpes qui permettent l’identification des anticorps les plus frequemment rencontres, anti-Jo1, PL7 et PL12. Les anti-SRP se reconnaissent egalement sur les coupes de tissus, mais l’aspect est tres voisin de celui que l’on observe avec les anti-ribosomes. L’identification des anti-ribosomes est actuellement facille a realiser, celle des anti-SRP reste encore limitee a certains laboratoires disposant des antigenes correspondants.

Primary biliary cirrhosis (PBC) is a chronic disease characterized by portal inflammation and necrosis of small intrahepatic bile ductules (1). PBC is an irreversible condition, and destruction of the bile ductules leads to progressive cholestasis and fibrosis, and may eventually lead to the development of cirrhosis. PBC is most likely an autoimmune disorder (2), and anti-mitochondrial antibody (anti-M2) has been a diagnostically very useful marker: several studies have reported a positivity rate for anti-M2 of >95% in biopsy-confirmed PBC patients (3). The major mitochondrial antigen was identified as the 74-kDa E2 subunit of the pyruvate dehydrogenase complex (PDC), a member of the 2-oxoacid dehydrogenase complex family (4). The traditional technique for the detection of anti-M2 is immunofluorescence (5), but recently new serological assays, such as ELISA, immunoblotting, and enzyme inhibition (EI), have been developed (6)(7). A miniaturized EI assay for performance on microtiter plates has already been described (8)(9). In this study we evaluated a new commercially available and completely automated EI assay manufactured by Trace Scientific (Victoria, Australia) and compared it to the immunofluorescence and ELISA techniques performed in our laboratory. The TRACE enzymatic procedure is a unique method based on the PDC inhibitory properties of the principal anti-74-kDa antibody. PDC catalyzes the following reaction: \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[\mathrm{Pyruvate}{+}\mathrm{NAD}^{\mathrm{{+}}}{+}\mathrm{CoA}\ \begin{array}{l}\mathrm{PDC}\\{\rightarrow}\end{array}\ \mathrm{Acetyl-CoA}{+}\mathrm{NADH}{+}\mathrm{H}^{{+}}{+}\mathrm{CO}_{2}\] \end{document} In the absence of anti-M2, this reaction will proceed at the maximal rate after the addition of a serum sample. If a sample contains anti-M2, the PDC activity will be inhibited, greatly reducing the rate of reaction, typically to

New treatment strategies require that rheumatoid arthritis (RA) be diagnosed as early as possible. New diagnostic markers were required, because rheumatoid factors (RF), until now criteria for classification of RA, are not sufficiently specific and sometimes appear late, thereby limiting their diagnostic usefulness. The objective of this review is to describe the current state of knowledge and more particularly to analyze the interest of new RA autoanti-bodies, called anti-peptide or anti-citrullinated protein anti-bodies (ACPA). Other autoanti-bodies have been described, including anti-Sa, anti-alpha enolase, and anti-calpastatin autoanti-bodies. Nonetheless, their diagnostic value remains limited compared to ACPA. Accordingly, in daily practice today, the only autoanti-bodies that must be tested for to diagnose RA are the ACPAs and RFs. The discovery of ACPA (initially called anti-keratin and anti-perinuclear anti-bodies) was a major step forward for the laboratory diagnosis of RA. The tests most often used routinely areenzyme-linked immunosorbent assays(ELISA) with cyclic citrullinated peptides, whence the name anti-CCP autoanti-bodies. Accordingly, the two terms ACPA and anti-CCP can both be used. The diagnostic value, in particular their specificity, is on the order of 95%, regardless of the method of identification. These markers are very useful and are often present earlier than RF. These ACPA also have prognostic value because they are associated with more aggressive forms of RA. On the other hand, their value over time, in particular, their fluctuation as a function of treatment, is more controversial. In practice, it is recommended to test for both RF and ACPA in a diagnostic work-up for early RA. During follow-up, the value of testing for these autoanti-bodies has not been demonstrated, but additional studies are still necessary with the anti-CCP autoanti-bodies and the new anti-citrullinated protein autoanti-bodies.

Anti-Saccharomyces cerevisiae antibodies (ASCA), anti-nuclear associated anti-neutrophil antibodies (NANA) and antibodies to exocrine pancreas (PAB), are serological tools for discriminating Crohn's disease (CrD) and ulcerative colitis (UC). Like CrD, coeliac disease (CoD) is an inflammatory bowel disease (IBD) associated with (auto) antibodies. Performing a multicenter study we primarily aimed to determine the performance of ASCA, NANA and PAB tests for IBD diagnosis in children and adults, and secondarily to evaluate the prevalence of these markers in CoD.Sera of 109 patients with CrD, 78 with UC, 45 with CoD and 50 healthy blood donors were retrospectively included. ASCA, NANA and PAB were detected by indirect immunofluorescence (IIF).ASCA+/NANA- profile displayed a positive predictive value of 94.2% for CrD. Detection of ASCA was correlated with a more severe clinical profile of CrD and treatment of the disease did not influence their serum levels. ASCA positivity was found in 37.9% of active CoD. PAB were found in 36.7% CrD and 13.3% CoD patients and were not correlated with clinical features of CrD, except with an early onset of the disease. Fifteen CrD patients were ASCA negative and PAB positive.ASCA and PAB detected by IIF are specific markers for CrD although their presence does not rule out a possible active CoD. The combination of ASCA, NANA and PAB tests improves the sensitivity of immunological markers for CrD. Repeating ASCA, NANA, and PAB testing during the course of CrD has no clinical value.

This article gives a summary of the history of vasculitis through early and past descriptions. Known, reported and depicted since time immemorial those diseases are quite polymorphous, depending on type and localization of the affected vessels. Clear classification criteria were finally laid down at the end of the XXth century giving a new impulse as well to the detection and the identification of specific biological markers as to the way to treat effectively those severe diseases.

Plusieurs types d’autoanticorps peuvent etre mis en evidence dans le serum des patients atteints de polyarthrite rhumatoide (PR). Le plus connu et le plus utilise est le facteur rhumatoide (FR) qui constitue encore un des sept criteres de classification de la PR de l’American College of Rheumatology. Cependant, si les FR sont des marqueurs sensibles, ils ne sont pas totalement specifiques de la PR. En revanche, les anticorps anti-proteines ou peptides citrulline(e)s sont recemment apparus comme ayant une bonne sensibilite et surtout une specificite tres elevee vis-a-vis de la PR. Ils permettent d’en poser le diagnostic de facon tres precoce et de predire les formes les plus agressives de la maladie qui necessitent une prise en charge adaptee.

Fodrin, an actin binding protein found in the cytoskeleton of most eukaryotic cells, would seem to be an important organ-specific autoantigen in Sjogren’s syndrome (SS). Fodrin is, moreover, detected in the salivary glands of patients with primary SS (pSS) but not in controls. It was thus recently claimed that antibodies against α-fodrin are a sensitive and specific serological marker for pSS.1 In this study we investigated the prevalence of autoantibodies against α-fodrin in patients with pSS, as compared with healthy subjects and patients with other autoimmune diseases. The study group included 107 patients with well defined pSS (mean age 57.5 years), 32 patients with systemic lupus erythematosus (SLE; mean age 40.1 years), 43 patients with rheumatoid arthritis (RA; mean age 59.0 years) with no signs of secondary SS, and 48 healthy blood donors (mean age 84.3 years). A diagnosis of SLE, RA, or pSS was …

The case of a patient who developed an acute dermatomyositis-like syndrome upon infection by Toxoplasma gondii is reported. Emphasis is given on the chronology of the anti-Toxoplasma IgM and IgG antibody rise, the muscle enzyme movements, the antinuclear antibody development in comparison to the clinical symptoms and their follow-up after Toxoplasma treatment. The close monitoring of the sequential clinical and biological pattern allows insights into the infectious and auto-immune diseases presented by this patient. Taking into account other reported cases and the clinical presentation of this patient some conclusions and recommendations are inferred.

According to international criteria, autoimmune hepatitis (AIH) type 1 is characterized by the presence of antinuclear or anti-smooth muscle antibodies (SMA) with F-actin specificity. SMA have been found in 85% of AIH patients, but are not specific to this disease, and anti-F-actin specificity is not always verified when SMA are detected. The objective of this study was to determine the diagnostic value of anti-F-actin antibodies in a large population. A multicenter study involving 12 clinical centers was performed. Patients were selected on the basis of the presence of F-actin SMA detected by indirect immunofluorescence (IIF) on rat liver-kidney-stomach sections and was confirmed by IIF on Hep2 cells treated with colchicine, or F-actin dot-blot. The clinical status of patients was determined from their medical records. One hundred sixty-eight patients were included: 76% women, 24% men; mean age of 45 years (range, 2-88 years), with a bimodal age distribution. Sixty percent had AIH type 1, and 40% had another disease. In the group of women younger than 25 years, 90% had AIH type 1. Other pathologies associated with antiactin were other liver diseases (19%), including viral hepatitis C (7%), and non-liver diseases (21%), including connective tissue diseases (12%). Antibody titers were higher in AIH than in other diseases. Antiactin antibodies are of major diagnostic value in AIH, especially in young women; they may be found in other disease settings, but mostly at low levels.

Objective: To determine whether anti-Ro52 is an independent serum marker in connective tissue disease. Methods: Over a two year period, 1727 consecutive antinuclear antibody (ANA) positive serum samples were analysed in parallel by double immunodiffusion with thymus/spleen nuclear extract and by line immunoassay with recombinant Ro52, recombinant La/SSB, and natural Ro60. Sera that were only reactive towards Ro52 were further analysed by a variety of additional anti-SSA/Ro detection methods and by specific anti-Ro52 and anti-Ro60 assays. Natural purified SSA/Ro was analysed by immunoblot and protein sequencing. Results: Analysis of natural purified SSA/Ro (Immunovision, Springdale, AR) showed only Ro60 and no immunoreactive Ro52. Consequently, assays based on this substrate only identify sera with anti-Ro60 reactivity. Twenty serum samples showed anti-Ro52 without anti-Ro60 and anti-SSB/La on line immunoassay. By additional testing, 2/20 sera were found positive for anti-Ro60 reactivity. The remaining 18 sera were not identified by any of the classical anti-SSA/Ro assays and were considered to be reactive only with Ro52 and not with Ro60. This anti-Ro52 reactivity was confirmed by natural and recombinant Ro52 in 16/18 cases. 12/18 sera corresponded to connective tissue diseases. Conclusion: Anti-Ro52 positive sera without any evidence of anti-Ro60 and anti-La/SSB reactivity can be considered as an independent group that is systematically missed by classical anti-SSA/Ro detection methods owing to a bias towards anti-Ro60 reactivity. The anti-Ro52 sera are precipitin negative, not retrieved by SSA/Ro enzyme linked immunosorbent assays (ELISAs) based on natural SSA/Ro, and show no specific ANA fluorescence staining pattern. These findings together with the clinical data indicate that anti-Ro52 should be considered as an additional and independent serum marker.

Background The nucleosome is considered as a major antigen in SLE and nucleosome-specific antibodies (Ab) seem to be the most specific and the earliest markers of SLE. Objectives To evaluate different methods of detecting anti-nucleosome Abs and determine the diagnostic value of these Abs in recently active SLE. Methods A 2 year (1998–99) prospective multicenter study in 13 European Immunopathology Centres (Groupe d’Etude de l’Auto-Immunite). Patients: (i) 55 cases of recently active SLE (evolution IgG anti-nucleosome Abs were detected by ELISA or immunodot using different nucleosome preparations. IgG anti-ds DNA Abs were detected by ELISA (calf thymus and human recombinant plasmid DNA). Results 34/55 SLE patients had anti-nucleosome Abs reacting with 4 kits. 16/55 SLE patients had anti-nucleosome Abs reacting with 1 to 3 kits. 5/55 SLE patients were negative for anti-nucleosome Abs. 5/50 patients with other autoimmune diseases had anti-nucleosome Abs. Conclusion 50/55 (91%) of patients with recently active SLE had anti-nucleosome Abs (by at least 1 method), 46/55 (84%) also had anti-ds DNA Abs (by ELISA). The sensitivity and the specificity of the anti-nucleosome Abs for SLE depend on the method and the nucleosome preparation.

Les anticorps diriges contre la membrane basale glomerulaire caracterisent un sous-groupe des glomerulonephrites rapidement progressives frequemment associees a des hemorragies pulmonaires realisant un syndrome pneumo-renal appele maladie de Goodpasture.La recherche des anticorps anti-membrane basale glomerulaire doit pouvoir etre realisee rapidement etant donne que la survie de la fonction renale depend de la precocite de l’instauration du traitement. Ces anticorps se recherchent par immunofluorescence indirecte sur des coupes de rein de primate prealablement traitees par l’uree ou par immunodot ou ELISA contre le determinant NCl α3 du collagene IV. Ces antoanticorps ont une specificite et une sensibilite superieure a 90 % pour la maladie de Goodpasture.

p330d/CENP-F is a novel proliferation-associated and cell cycle-dependent centromere autoantigen which appears to play a very important role in mitotic progression. As an initial step in exploring the clinical and biological significance of autoantibodies to this protein, we evaluated the clinical histories of 26 patients producing these antibodies. The antibodies were detected by both indirect immunofluorescence microscopy (IIF) and Western blotting. All the sera contained anti-p330d/CENP-F IgG antibodies, with an average titer by IIF of 1:6,917 (range 1:160 to 1:20,480). Most of the patients had disorders associated with abnormal or increased cell proliferation at the time the anti-p330d/CENP-F antibodies were detected. These included cancers of various types (14), chronic liver disease (3), chronic rejection of renal allografts (2), and Crohn's disease (1). The average IIF titer of the anti-p330d/CENP-F antibodies in the patients with cancer, 1:10,103, was significantly higher than the average titer in non-cancer patients, 1:3,200 (P = 0.008). Autoimmunity to p330d/CENP-F appeared not to be associated with rheumatic diseases, in particular scleroderma, since only three of the 26 patients had rheumatic disease and the antibodies were not detected by IIF in a group of 351 patients with scleroderma and related disorders. Our findings, although retrospective and limited to a relatively small number of patients, point to the hypothesis that autoimmunity to p330d/CENP-F could be related to events involving increased or abnormal cell proliferation.

Le terme d’anticorps anti-nucleaires (ANA), consacre par l’usage, est trop restrictif puisque certains de ces anticorps reconnaissent des antigenes cytoplasmiques. Un tres grand nombre d’ANA a ete identifie au cours des 30 dernieres annees.

Anti-filaggrin autoantibodies (AFA) are highly specific markers for rheumatoid arthritis (RA) and can be detected by immunoblotting using human epidermal protein extracts. Furthermore, it was demonstrated that citrullination of the filaggrin epitopes is crucial for epitope recognition and that citrullinated peptides are also recognized by these specific autoantibodies. Based on these data, a line immunoassay (LIA) was developed containing as individual markers in vitro citrullinated recombinant filaggrin and two citrullinated synthetic peptides. Firstly, a comparison was made between this prototype LIA and the AFA blot using natural filaggrin. A blind serum panel consisting of 25 early RA, 25 longstanding RA, and 25 disease controls was selected. Results showed a similar performance of both tests at a specificity level of 95%, while the LIA proved significantly better (P = 0.035) than the AFA blot at 99% specificity. At the latter specificity level, 2 out of 17 RF negative samples were retrieved on LIA but not on Western blot. The LIA was further evaluated on sera obtained from 335 RA patients and 254 patients with non-RA rheumatological disorders in a retrospective study. The overall sensitivity of the LIA including three markers (LIA3) was 65.1% versus 61.8% if only the reactivity towards the citrullinated peptides was considered (LIA2). The specificity of LIA3 was 97.6% versus 98.4% for LIA2, which correlates with an estimated positive predictive value (PPV) of 87.3% for LIA3 and 90.7% for LIA2. Thirty-seven percent (30/81) of the RF-negative RA samples proved LIA2-positive, while 52 out of 55 RF positive control samples were negative for anti-filaggrin. Higher specificity and sensitivity was obtained for LIA2 in comparison with anti-RA33 immunoblot, whereas good agreement could be observed with anti-keratin antibody (AKA) testing. In conclusion, anti-filaggrin autoantibodies can be readily detected by a LIA test based on citrullinated peptides, resulting in a high specificity and hence high PPV for RA. The assay can serve as a user-friendly alternative for AKA immunofluorescent and immunoblot techniques. Together with the RF complementarity, this test provides a valuable tool in the differential diagnosis of RA.

A case of severe angioedema with several episodes of life-threatening attacks during a follow-up of 7 years is presented. Although the biologic profile is that of an acquired C1 INH deficiency, no lymphoproliferative malignancy or immune-complex disease could be proven until now. However, the patient has had a small monoclonal IgG lambda-gammopathy for 4 years. During the last 4 years, edematous manifestations have stopped. The patient now suffers at regular intervals of about a week from short-lasting attacks with digestive and vasomotor symptoms. This clinical evolution is accompanied by a worsening in the complement abnormalities. The digestive and vasomotor attacks were found to be correlated with sudden prekallikrein and high-molecular-weight kininogen consumption. These findings demonstrate that prekallikrein is activated during acquired C1 INH deficiency and that the products of this pathway such as bradykinin are probably responsible for a part of the clinical manifestations associated with this disorder.