Presence Of Other Autoantibodies Research Articles

The Discrepancy of ANA and Compartment Bead Patterns Suggestive of a Neuropsychiatry Systemic Lupus Erythematosus (NPSLE)

Neuropsychiatric systemic lupus erythematosus (NPSLE) exhibits neurological and psychiatric manifestations in systemic lupus erythematosus (SLE) patients, which NPSLE diagnosis can be challenging for rheumatologists. An Indonesian female, 44 years old, complained of two times seizures with 10-min duration, which during seizures were stiff, eyes rolled up, foaming at the mouth, wet the bed, and fainting afterward. The patient also has a history of SLE and received cyclophosphamide therapy 5 years ago. Her clinical condition showed facial and lingual palsy, with central type on the right. Antinuclear antibody indirect immunofluorescence (ANA IF) positive using cytobead ANA with a homogenous pattern and cytoplasmic speckled titer 1/80. Confirmation beads showed positive of dsDNA only. ANA profile showed positive antinucleosome, antihistone, and AMA-M2, and also increased anticardiolipin antibody that supports the diagnosis of NPSLE. The difference in the pattern of ANA IF with confirmation beads suggests the presence of other autoantibodies in NPSLE.

Antibodies to histone in the pediatric population: a retrospective chart review

BackgroundAntibodies to histone have been associated in the adult literature with systemic lupus erythematosus(SLE) and drug induced lupus(DILE). Little data is available regarding the spectrum of pathology that antibodies to histone encompass in the pediatric population. Prior studies suggest an association with SLE, juvenile idiopathic arthritis(JIA), uveitis and linear scleroderma.MethodsPatient charts were reviewed that contained positive anti-histone antibody testing during a consecutive three year period. Patient diagnosis along with the presence of: anti-histone antibody titer, ANA, and the presence of other autoantibodies to SSA, SSB, Sm, RNP, dsDNA and chromatin were obtained. The frequency of SLE, JIA and DILE was further investigated in specific subsets.Results139 individual charts were reviewed containing 41 different diagnoses. The most common diagnosis was hypermobility arthralgia with 22 patients. The most frequent rheumatologic diagnosis was JIA(nonsystemic) with 19. 13 patients in this study were diagnosed with SLE and 2 with DILE. 18 patients had other autoantibody production, of these, 11 had SLE or DILE. Only one of 62 patients with a weak antihistone antibody titer(1.0-1.5) was diagnosed with SLE. When strong titers are present(> 2.5), the antihistone antibody test was associated with a greater than 50% incidence of an underlying rheumatologic disease and ten times higher incidence of SLE than a weak titer. In regards to the frequency of SLE, there was a statistically significant difference between weak and moderate titers and between weak and strong titers.ConclusionThe presence of anti-histone antibody was observed in a variety of diagnoses in the pediatric population. Overall, the presence of anti-histone antibodies appears to have poor diagnostic utility for any specific condition. However, diagnostic utility for SLE does appear to improve with higher titers, when combined with other autoantibody positivity. Strength of titer did not appear to be a factor for JIA, but was the most frequently observed rheumatologic disease in this study.

Clinical significance of anti-NT5c1A autoantibody in Korean patients with inflammatory myopathies.

To explore the clinical significance of anti-cytosolic 5'-nucleoditase 1A (NT5c1A) antibody seropositivity in inflammatory myopathies, we measured anti-NT5c1A antibodies and analyzed their clinical features. Anti-NT5c1A antibodies were measured in the sera of 103 patients with inflammatory myopathies using an enzyme-linked immunosorbent assay. Positivity for anti-NT5c1A antibody was found in 13 (12.6%) of 103 patients with inflammatory myopathy. Anti-NT5c1A antibody was most frequently identified in patients with inclusion body myositis (IBM) (8/20, 40%), followed by dermatomyositis (2/13, 15.4%), immune-mediated necrotizing myopathy (2/28, 7.1%), and polymyositis (1/42, 2.4%). In eight patients with the anti-NT5c1A antibody-seropositive IBM, the median age at symptom onset was 54 years (interquartile range [IQR]: 48-57 years), and the median disease duration was 34 months (IQR: 24-50 months]. Knee extension weakness was greater than or equal to hip flexion weakness in eight (100%) patients, and finger flexion strength was less than shoulder abduction in three (38%) patients. Dysphagia symptoms were found in three (38%) patients. The median serum CK level was 581 IU/l (IQR: 434-868 IU/L]. Clinically significant differences were not found between anti-NT5c1A antibody-seropositive and seronegative IBM groups with respect to gender, age at symptom onset, age at diagnosis, disease duration, serum CK values, presence of other autoantibodies, dysphagia, and the pattern of muscle impairment. Although anti-NT5c1A antibody is known to be associated with IBM, seropositivity has also been noted in non-IBM inflammatory myopathies, and is insufficient to have clinical significance by itself. These findings have important implications for interpreting anti-NT5c1A antibody test results as the first study in Korea.

Detection of circulating IgG autoantibody to FcεRIα in sera from chronic spontaneous urticaria patients.

Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by itchy wheals of at least 6 weeks in duration, wherein the autoimmune mechanism is involved to activate IgE receptors (FcεRIα) on mast cells. We aimed to assess levels of IgG autoantibody against FcεRIα in sera from CSU patients using dot-blot immunoassay. We performed a hospital-based cross-sectional study of 125 CSU patients (64 ASST-positive, 61 ASST-negative) and 64 age-and sex-matched healthy controls. The cut-off value of IgG FcεRIα autoantibody was determined as the mean intensity plus two standard deviations of values in controls. Positivity for IgG autoantibody to FcεRIα was analyzed according to clinical parameters of disease duration, urticaria activity score (UAS), ASST, response to antihistamine treatment, complement levels, and the presence of other autoantibodies. Nonparametric tests were applied for statistical analyses. IgG positivity to FcεRIα was noted in 24.8% of CSU patients and was significantly more frequent in ASST-positive patients than in ASST-negative patients (32.8% vs 16.4%, P=0.040). Only 3.1% of healthy controls had this autoantibody. Complement 3 levels were significantly lower in anti-FcεRIα antibody-positive patients than antibody-negative patients (109.8±19.9 vs 123.1±30.9, P=0.035). No significant associations were found between IgG positivity to FcεRIα and UAS, serum total IgE levels, atopic status, clinical responses to antihistamines, or the presence of anti-thyroid and anti-nuclear antibodies. These findings suggest that circulating IgG autoantibody to FcεRIα in a subset of patients may be involved in the autoimmune mechanism of CSU. Further studies are needed to clarify its clinical significance.

Genetics of Autoimmune Thyroiditis in Type 1 Diabetes Reveals a Novel Association With DPB1*0201: Data From the Type 1 Diabetes Genetics Consortium.

BACKGROUNDAutoimmune thyroiditis occurs in 10–25% of patients with type 1 diabetes (T1D). Most of these patients are also positive for thyroid peroxidase (TPO) antibodies. Thyroid dysfunction complicates T1D metabolic control and is a component of the autoimmune polyglandular syndrome (APS, type 2 or 3). Previous studies of isolated T1D and of T1D combined with other autoimmune disorders showed genetic susceptibility for alleles in HLA-DQB1 and -DRB1 and also CTLA4 and PTPN22.RESEARCH DESIGN AND METHODSWe analyzed the Type 1 Diabetes Genetics Consortium Autoantibody Workshop data by differentiating those T1D probands with and without TPO antibodies or thyroid disease with respect to polymorphisms in HLA, CTLA4, INS, PTPN22, and VDR, taking into account the ethnic origin. Genotype and clinical/immunogenic phenotype data were analyzed by gene counting methods and logistic regression analysis.RESULTSThe presence of TPO antibodies (25.2%) and thyroid disease (8.4%) was associated with older age, female sex, and presence of other autoantibodies (GAD65, ATPase, 21-OH) (all P < 0.001). The highest prevalence was in patients of Hispanic ancestry (31%) and the lowest in those of African ancestry (8%). In T1D non-Hispanic whites, HLA-DRB1*0101 is significantly (P < 0.0001) less frequent in TPO-positive than in TPO-negative individuals, whereas HLA-DRB1*0404, -DQB1*0301, and -DPB1*0201 are significantly (P < 0.0001) more frequent. Subjects with a high titer of TPO autoantibodies and with thyroid disease were associated with female sex and older age and negatively associated with DRB1*0401-DQB1*0302 (P < 0.0001). No significant differences were observed for an association of TPO positivity or thyroid disease with single nucleotide polymorphisms in the INS, CTLA4, or VDR loci, with nominal significance (P = 0.01) for PTPN22 R620W variant.CONCLUSIONSThyroid autoimmunity is highly prevalent in T1D patients of non-Hispanic white, Asian, or Hispanic origin. The strongest disease risk is conferred by female sex and older age. This risk is modulated by HLA-DRB1 and HLA-DPB1 loci. The immunogenetic profile for T1D with thyroid autoimmunity may identify distinct pathways regulating polyglandular autoimmunity and disease.

FRI0261 Anti-phospholipid antibodies in systemic sclerosis: Prevalence and clinical correlations

BackgroundAnti-phospholipid antibodies (APLA) are typically associated with thrombosis in systemic lupus erythematosus and anti-phospholipid syndrome. However, little is know about the clinical associations of these antibodies in systemic sclerosis (SSc).ObjectivesWe...

Aquaporin-4 antibody–positive cases beyond current diagnostic criteria for NMO spectrum disorders

To analyze aquaporin-4 (AQP4) antibody-positive patients who do not fulfill the current diagnostic criteria of neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSD). We used a cell-based assay (CBA) with AQP4-transfected cells to detect AQP4 antibody in 298 consecutive patients with inflammatory CNS disorders seen at Tohoku University Hospital from 2007 to 2012. The patients were diagnosed as NMO, NMOSD, multiple sclerosis, or others using the respective current diagnostic criteria. The seropositive samples by CBA were also tested using a commercial ELISA. Seventy-two patients were AQP4 antibody positive. Among them, 18.1% (13/72) did not meet the NMO or NMOSD criteria (7 with monophasic optic neuritis, 2 with attacks restricted to the brainstem, and 4 with myelitis with less than 3 vertebral segments) and 84.6% (11/13) of these had only a single attack. The ELISA results were negative in 38.4% (5/13) of those patients, and they had lower antibody titers by CBA than patients with NMO/NMOSD. Although these patients had a shorter follow-up and few attacks, they shared some clinical features with NMO/NMOSD patients such as onset age, female predominance, presence of other autoantibodies, severe optic neuritis attacks, centrally located spinal cord lesions, persisting hiccups, and nausea or vomiting episodes. AQP4 antibody-positive patients with single or recurrent attacks of optic neuritis, myelitis, or brain/brainstem disease not fulfilling the current criteria of NMO or NMOSD may not be uncommon, and they should also be included in the NMO spectrum.

The relevance of antigen binding to the pathogenicity of lupus autoantibodies

Although lupus autoantibodies provide diagnostic value, discordance between serum levels and nephritis poses mechanistic questions. Krishnan and co-workers report that only those that crossreact with basement membrane components produce immune deposits. Thus, other glomerular binding properties probably define where deposits form. Thereafter, Fc- and complement-mediated events influence disease expression. Clearly other factors determine the ultimate phenotype; however, the findings provide insights into the variable disease patterns in lupus nephritis.

Risk factors for ANA positivity in healthy persons.

IntroductionThe finding of antinuclear antibody (ANA) positivity in a healthy individual is usually of unknown significance and in most cases is benign. However, a subset of such individuals is at risk for development of autoimmune disease. We examined demographic and immunological features that are associated with ANA positivity in clinically healthy persons to develop insights into when this marker carries risk of progression to lupus.MethodsBiological samples from healthy individuals and patients with systemic lupus erythematosus (SLE) were obtained from the Dallas Regional Autoimmune Disease Registry (DRADR). Measurements carried out on serum samples included ANA, extractable nuclear antibodies (ENA) and autoantibody profiling using an array with more than 100 specificities. Whole blood RNA samples from a subset of individuals were used to analyze gene expression on the Illumina platform. Data were analyzed for associations of high ANA levels with demographic features, the presence of other autoantibodies and with gene expression profiles.ResultsOverall, ANA levels are significantly higher in females than in males and this association holds in patients with the autoimmune diseases lupus and rheumatoid arthritis (RA) as well as in healthy controls (HC). Age was not significantly associated with ANA levels and the elevated ANA values could not be explained by higher IgG levels. Another autoantibody, anti- cyclic citrullinated peptide (CCP), did not show gender dimorphism in rheumatoid arthritis (RA) or healthy individuals. The autoantigen array showed significant elevations of other autoantibodies in high ANA HCs. Some of these autoantibodies were directed to antigens in skin and others were related to autoimmune conditions of kidney, thyroid or joints. Gene expression analyses showed a greater prevalence of significantly upregulated genes in HCs with negative ANA values than in those with significant ANA positivity. Genes upregulated in high ANA HCs included a celiac disease autoantigen and some components of the Type I interferon (IFN) gene signature.ConclusionsRisks for ANA positivity include female gender and organ-specific autoimmunity. Upregulation of skin-specific autoantibodies may indicate that early events in the break of tolerance take place in cutaneous structures. Some of these changes may be mediated by Type I IFN. Blood profiling for expressed autoantibodies and genes has the potential to identify individuals at risk for development of autoimmune diseases including lupus.

Early Relapse of Autoimmune Glomerulonephritis After Kidney Transplantation Despite Antibody Induction and Triple-Drug-Based Immunosuppression

Early Relapse of Autoimmune Glomerulonephritis After Kidney Transplantation Despite Antibody Induction and Triple-Drug-Based Immunosuppression

A Common Nonsynonymous Single Nucleotide Polymorphism in the SLC30A8 Gene Determines ZnT8 Autoantibody Specificity in Type 1 Diabetes

OBJECTIVE—Zinc transporter eight (SLC30A8) is a major target of autoimmunity in human type 1A diabetes and is implicated in type 2 diabetes in genome-wide association studies. The type 2 diabetes nonsynonymous single nucleotide polymorphism (SNP) affecting aa325 lies within the region of highest ZnT8 autoantibody (ZnT8A) binding, prompting an investigation of its relationship to type 1 diabetes.RESEARCH DESIGN AND METHODS—ZnT8A radioimmunoprecipitation assays were performed in 421 new-onset type 1 diabetic Caucasians using COOH-terminal constructs incorporating the known human aa325 variants (Trp, Arg, and Gln). Genotypes were determined by PCR-based SNP analysis.RESULTS—Sera from 224 subjects (53%) were reactive to Arg325 probes, from 185 (44%) to Trp325probes, and from 142 (34%) to Gln325probes. Sixty subjects reacted only with Arg325 constructs, 31 with Trp325 only, and 1 with Gln325 only. The restriction to either Arg325 or Trp325 corresponded with inheritance of the respective C- or T-alleles. A strong gene dosage effect was also evident because both Arg- and Trp-restricted ZnT8As were less prevalent in heterozygous than homozygous individuals. The SLC30A8 SNP allele frequency (75% C and 25% T) varied little with age of type 1 diabetes onset or the presence of other autoantibodies.CONCLUSIONS—The finding that diabetes autoimmunity can be defined by a single polymorphic residue has not previously been documented. It argues against ZnT8 autoimmunity arising from molecular mimicry and suggests a mechanistic link between the two major forms of diabetes. It has implications for antigen-based therapeutic interventions because the response to ZnT8 administration could be protective or immunogenic depending on an individual's genotype.

Factores clínicos y epidemiológicos asociados con nefritis lúpica en pacientes del noroccidente colombiano

A cross-sectional and multicenter study was undertaken to analyze the clinical and immunological characteristics at diagnosis associated with nephritis in northwestern Colombian patients with systemic lupus erythematosus (SLE). Thirty-nine patients with lupus nephritis were included and were compared to 100 SLE patients without nephritis. A multivariate analysis was performed. The patients who developed nephritis had a higher frequency of oral ulcers (41% vs. 21%, OR = 3.1, 95% CI: 1.3-7.5 p = 0.01) and malar erythema (77% vs. 45%, OR = 4.4, 95% CI: 1.8-10.8 p = 0.001). Lupus nephritis was observed in 77% of cases during the first year of the disease. The frequency of anti-DNA antibodies was higher in patients with nephritis, however, differences were not statistically significant (83% vs 64%, OR = 2.6, 95% CI: 1.03-6.41, p = 0.06). The presence of other autoantibodies (anti-Ro, anti-La, anti-RNP, anti-Sm and anticardiolipin) at diagnosis was similar in both groups. This autoantibody profile remained unchanged throughout the evolution of the disease. Patients with lupus nephritis had a higher prevalence of arterial hypertension (60% vs 10%, OR = 13.7, 95% IC: 5-37, p = 0.00001) and hyperlipidemia (30% vs 7%, OR = 8.1, 95% IC: 2.5-27, p = 0.0006) at onset. Finally, patients with lupus nephritis required more hospitalizations (> 1) over the course of disease (89% vs 60%, OR = 7.8, 95% CI: 2.1-29, p = 0.002). In conclusion, lupus nephritis appears early during the course of SLE. Malar erythema, oral ulcers, hypertension and hyperlipidemia at onset of disease are associated factors. Lupus nephritis is a major risk factor leading to repeated hospitalizations. This study may help to assist in public health policies in our population in order to improve patient outcomes while simultaneously reducing disease costs.

Ocular features associated with anticardiolipin antibodies: A descriptive study

PURPOSE: To evaluate ocular features in patients presenting with inflammation in the presence of anticardiolipin antibodies. METHODS: A descriptive study of 13 patients presenting with idiopathic ocular inflammation involving anterior and posterior segment was performed. Patients were followed for a mean follow-up of 22 months (range, 1 to 125). A comprehensive report of ocular involvement, including visual symptoms, visual acuity, clinical characteristics, funduscopic and fluorangiographic features, was reported. Systemic associated symptoms were analyzed. Laboratory investigations included anticardiolipin antibody titers and isotypes, presence of other autoantibodies, and markers of immune system activation. RESULTS: The most common ocular symptom at presentation was blurred vision (eight patients) followed by redness and pain(three patients) and visual loss(two patients). Anterior segment abnormalities, including iritis (eight patients) scleritis (two patients) and filamentary keratitis (one patient), were present in 76% of patients, whereas the most represented feature of posterior involvement was retinal vasculitis (60%) followed by vitritis (38%), retinal detachment (15%), posterior scleritis (7%), and central retinal artery occlusion (7%). All patients had abnormal titers of anticardiolipin antibodies, predominantly IgG isotype; six had markers of immune system activation. CONCLUSIONS: Although posterior pole disease is more commonly associated with anticardiolipin antibodies, the anterior segment can also be involved with a wide spectrum of features. Scleritis has never been previously described as associated with anticardiolipin antibodies. Systemic symptoms are frequently present in association with ocular disease.

Anticardiolipin antibodies in patients with chronic hepatitis C virus infection: characterization in relation to antiphospholipid syndrome.

The antiphospholipid syndrome (APS) is usually defined by the association of clinical manifestations that comprise venous and/or arterial thrombosis, recurrent fetal losses, and thrombocytopenia, along with the presence of anticardiolipin (aCL) antibodies and/or lupus anticoagulant. Various infectious diseases can induce aCL; however, these antibodies are not usually associated with thrombotic events, as happens with autoimmune diseases, in which these antibodies need the presence of beta(2)-glycoprotein I. Levels of immunoglobulin G (IgG) and IgM aCL antibodies were determined by enzyme-linked immunosorbent assay for 243 patients with chronic hepatitis C virus (HCV) infection and 100 healthy controls. Clinical events of APS, the level of beta(2)-glycoprotein dependence of aCL, the presence of cryoglobulins and other autoantibodies, and cross-reactivity between purified aCL and HCV were evaluated. Positive results for aCL antibodies were found more frequently (3. 3%) for the patients with HCV infection than for healthy controls (0%). All positive aCL antibodies were beta(2)-glycoprotein I independent. No significant association was found between aCL antibodies and clinical manifestations of APS, neither was one found between the presence of other autoantibodies or cryoglobulins and that of aCL. Finally, no cross-reactivity between aCL antibodies and HCV antigens was observed. As previously reported, aCL antibodies seem to be an epiphenomenon, and they do not have clinical or laboratory significance in HCV patients.

Adrenal autoantibodies and organ-specific autoimmunity in patients with Addison's disease.

Autoimmune destruction of the adrenal gland is the major cause of Idiopathic Addison's disease, but the significance of 21-hydroxylase autoantibodies and their correlation with the presence of other autoantibodies have not so far been investigated in a larger population of patients with Addison's disease. We have now characterized a cohort of patients with idiopathic Addison's disease (n = 97) regarding the specificity of autoantibodies against the adrenal cortex and, as Addison's disease can be either an isolated condition or part of a polyendocrine disorder, we investigated the presence of organ-specific polyendocrine autoimmunity in this patient population. Cross-sectional study. Autoantibodies were analysed with indirect immunofluorescence (IF) on tissue preparations, ELISA and in Western blots using bacterially expressed proteins. Eighty-four per cent (81/97) of the patient sera recognized the steroid-producing cells of the adrenal cortex in indirect IF. The antigen was identified as 21-hydroxylase by 72% (70/97) of the patient sera in Western blots. Seven sera that were negative on adrenocortical IF identified 21-hydroxylase on Western blot, while eight IF-positive sera were 21-hydroxylase-negative. Five sera weakly recognized 17 alpha-hydroxylase in Western blots, but all of these were also positive for 21-hydroxylase. In 13 cases (12 women), the sera also reacted with testicular Leydig cells, and nine of these identified the side-chain cleavage (SCC) enzyme. Other clinically evident organ-specific autoimmune disorders were present in 40% of the 97 patients and abnormal titres of organ-specific antibodies were found in 60% of the patients. In idiopathic Addison's disease, auto-antibodies against 21-hydroxylase are found in a majority of cases and this represents an important diagnostic tool. The enzyme 17 alpha-hydroxylase does not seem to constitute a major autoantigen in Addison's disease. In a subgroup of patients with autoantibodies to gonads, antibodies to SCC are produced, often in parallel with antibodies to 21-hydroxylase. In yet another subgroup the specificity of autoantibodies giving positive immunofluorescence is still unknown. Three patients revealed a polyendocrine syndrome which clinically resembles autoimmune polyendocrine syndrome (APS) type I, but serologically corresponds to APS type II. Polyendocrine disorders are often associated with Addison's disease, and screening, including quantification of autoantibodies, may help to identify those at risk of developing associated autoimmune disorders.

Thyroid autoimmune disorders in patients with chronic hepatitis C before and during interferon‐α therapy

Hepatitis C virus is involved in the induction of autoimmunity and interferon can also induce hepatic and non-hepatic autoimmune reactions. This study assessed the prevalence of thyroid autoantibodies and autoimmune thyroid disorders in patients with chronic hepatitis C before and during interferon therapy. We studied prospectively 207 patients positive for anti-HCV and viral RNA. One hundred and forty-four of them received a therapeutic trial of one year with interferon-alpha. Free thyroxine, TSH and autoantibodies to thyroglobulin and thyroid microsomes were systematically tested at entry and at weeks 12 and 24 in both untreated and treated patients. Sixteen of the 207 patients (7.7%) had thyroid dysfunction, including positive antithyroid antibodies in 14 (6.7%) and hypothyroidism in 10 (4.8%) prior to interferon therapy. In addition, during pretreatment evaluation one patient developed clinical hyperthyroidism after transient subclinical hypothyroidism and another had subclinical hyperthyroidism. Prevalences of positive antithyroid antibodies and hypothyroidism were significantly higher in women (14.7 and 10.5%, respectively, vs 0% in men, P < 0.01) and were directly associated with increasing age (P < 0.01). The incidence of thyroid dysfunction was also significantly higher in patients with other autoantibodies such as anti-nuclear (ANA) (P < 0.01). A trial with interferon was initiated in 144 patients and 8 of 142 (5.6%) without previous thyroid abnormalities developed thyroid dysfunction, including positive antithyroid antibodies in 7 (4.9%) and hypothyroidism in 4 (2.8%) with a prevalence again significantly higher in women (12.7 and 8.3%, respectively, vs 1% in men, P < 0.01) and also directly related to increasing age (P < 0.01). An association was found between the development of thyroid dysfunction during interferon therapy and the presence of other autoantibodies, including ANA, anti-DNA and anti-Sjögren's antibodies (P < 0.01), as well as with the induction of autoimmune hepatitis and Sjögren's syndrome (P < 0.01 and < 0.05 respectively). Thyroid abnormalities were reversed in all patients when interferon therapy was discontinued. No significant association was found between chronic hepatitis C and the presence of thyroid autoimmunity in female patients. On the contrary, interferon therapy induced antithyroid autoantibodies and thyroid dysfunction de novo in patients with chronic hepatitis C without pre-existing thyroid abnormalities. Thyroid dysfunction secondary to interferon was reversible after discontinuation of therapy.

Circulating Fcγ receptor-specific autoantibodies in localized and systemic scleroderma

Background: Anti-Fcγ receptor (anti-FcγR) autoantibodies occur in patients with systemic scleroderma. Their clinical significance is unknown. Objective: Our purpose was to determine the incidence of anti-FcγR autoantibodies in patients with localized and systemic scleroderma and to examine there lation between these autoantibodies, the severity of the disease, and the presence of other autoantibodies. Methods: Patients were placed into three clinical groups: three had diffuse systemic scleroderma, 47 had limited systemic scleroderma, and nine had localized systemic scleroderma. Antinuclear antibody titer and pattern were measured by indirect immunofluorescence with human epithelial (HEp)-2 cells and tissue sections, whereas anti-Scl-70 antibodies were measured by gel diffusion technique. Anti-FcγR autoantibodies were measured in serum from patients and from 25 healthy persons by enzyme-linked immunosorbent assay with human recombinant FcγRII (CD32) and FcγRIII (CD16). Results: Anti-FcγR autoantibodies were detected in 54% of patients and in none of the healthy control subjects. Autoantibodies were present in all three clinical groups and were most frequently directed against FcγRIII. Correlation between patients' clinical and laboratory data and anti-FcγR autoantibodies could not be demonstrated. Conclusion: The presence of anti-FcγR autoantibodies in the serum of patients with either systemic or localized scleroderma and the lack of these autoantibodies in healthy persons suggest that they may play a role in the pathogenesis of these diseases.

An audit of ANCA in routine clinical practice.

We have reviewed the medical records of 301/327 consecutive patients in whom anti-neutrophil cytoplasmic antibodies (ANCA) were detected by the Regional Immunology Laboratory in Northern Ireland between January 1988 and October 1991 (45 months). We have collected data for each patient regarding age, sex, smoking habit, area of residence, and details of any other autoantibody activity. Clinical diagnosis was established, with the number of organ systems involved and the evidence for that involvement (symptomatic, biochemical, radiological, and histological). Diagnoses were divided into four groups according to their recognised vasculitic features and these were related to the pattern of immunofluorescence and maximum ANCA titre detected. The most frequent diagnosis was rheumatoid arthritis (18.2% of patients) and the connective tissue disorders as a whole accounted for 27.9% of patients. ANCA were also detected in a wide range of clinical conditions which are not associated with vasculitis and these patients were an important source of 'false-positives'. The positive predictive value (PPV) of ANCA of all patterns and titres for vasculitic conditions was 27%, however, the detection of a classical ANCA pattern at high titre (> or = 1:640) was associated with an increased PPV of 75%. The coexistence of an antinuclear antibody (ANA) reduces the PPV of both classical and perinuclear ANCA, although perinuclear ANCA with antimyeloperoxidase specificity had an improved PPV. We conclude that ANCA testing should not be used as the only screening investigation for vasculitis but should be included in a rational investigative scheme. The interpretation of a positive ANCA result must take into account the presence of other autoantibodies and the full range of non-vasculitic conditions when the clinical situation is not typical of vasculitis.

Presence of Anti-La (SS-B) Is Associated with Binding to the 13-kD Carboxyl Terminus of 60-kD Ro(SS-A) in Systemic Lupus Erythematosus

In systemic lupus erythematosus (SLE) clinical manifestations, autoantibody production, and immunogenetics are inter-related. The ability to study parts of the autoimmune response may allow a more detailed understanding of these relationships. We undertook this study to determine whether the fine specificity of the autoimmune response to 60-kD Ro(SS-A) was related to the presence of other autoantibodies. We screened 74 patients with SLE for antibodies to the carboxyl 13-kD terminal of 60-kD Ro(SS-A) (13 kD). Twenty-five sera had such antibodies. This reactivity was distinguished by the presence of not only anti-Ro(SS-A) but also other antibodies. All nine sera with Ro(SS-A) and La(SS-B) Ouchterlony immunodiffusion precipitins bound 13-kD (p = 0.01), whereas 10 of 11 sera with both anti-Ro(SS-A) and anti-La(SS-B) as determined by immunosorbent assay bound 13-kD (p = 0.002). Inhibition studies demonstrated that antibodies binding the 13-kD fragment bound the 60-kD Ro(SS-A) protein but did not bind the La(SS-B) protein. Thus, anti-La(SS-B) was found in those sera that bound epitopes within the 13-kD carboxyl terminal of 60-kD Ro(SS-A). These data suggest a structural basis by which anti-Ro(SS-A) and anti-La(SS-B) are coupled in SLE.

Anti-Thyroid Peroxidase Antibodies in Thyroid Disorders and Non-Thyroid Autoimmune Diseases

A new commercial method for measurement of anti-thyroid peroxidase (anti-TPO DYNOtest, Henning, Berlin) was evaluated in normal subjects and in patients with autoimmune thyroid and non-thyroid diseases, and compared to an immune fluorescence method for measurement of anti-microsomal antibodies (MicAb), and a radioimmunological method for quantifying thyroglobulin antibodies (TgAb). The majority of normal subjects had anti-TPO levels below 52 U/ml and patients with Hashimoto's thyroiditis had levels above 200 U/ml, with a good correlation to MicAb. In other autoimmune thyroid diseases the correlation was less pronounced. In non-thyroid autoimmune diseases MicAb showed falsely positive reactions in the presence of other autoantibodies, e.g. mitochondrial antibodies. The present study indicates that the anti-TPO method should probably replace measurements of MicAb for routine clinical use, thus providing a sensitive, precise, antigen specific method with the ability to reveal quantitative fluctuations. The study also indicates that TgAb could be abolished in routine diagnosis of autoimmune thyroid diseases and be reserved for special clinical situations, research purposes as well as measurement in sera before evaluation of serum thyroglobulin levels.