Incidence Of Antinuclear Antibodies Research Articles

Mild-to-moderate COVID-19 does not predispose to the development of autoimmune rheumatic diseases or autoimmune-based thrombosis.

An infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2) may have a significant impact on the human immune system. Interactions between the virus and defence mechanisms may promote the development of autoimmune processes which manifest as antinuclear antibody (ANA) synthesis. Since many different viruses are suspected to take part in the pathogenesis of different systemic autoimmune rheumatic diseases (SARDs), we examined whether coronavirus disease 2019 convalescents who suffer from mild to moderate disease have a higher risk of developing ANA and anti-β2-glicoprotein I IgG antibodies (β2 GPI). In a retrospective study, we examined 294 adults among volunteer blood donors divided into convalescents (N = 215) and healthy controls (N = 79). For ANA detection, we used line-blotting, a type of indirect immunofluorescence assay (IF), to determine antigenic specificity and ELISA for β2 GPI. We found a lower incidence of ANA in convalescents than in healthy controls, with the majority of these antibodies directed to antigens with no known clinical significance. Additionally, no participants were positive for β2 GPI in either group. Our results show that COVID-19 with mild to moderate symptoms in the generally healthy population does not induce the development of ANA or anti-β2 GPI antibodies for at least 6 months following the disease.

P–354 Analysis of pregnancy and miscarriage rates in anti-centromere antibodies (ACA)-positive patients treated with ART

Abstract Study question Do ACA have an effect on pregnancy and miscarriage rates of human embryos? Summary answer The present results suggest that in ACA-positive cases, the pregnancy rate per transfer was significantly lower, although the miscarriage rate was not affected. What is known already We have previously shown that patients with high levels of anti-centromere antibody (ACA), (one of the anti-nuclear antibodies (ANA)), frequently have dispersal of the female chromosomes in the cytoplasm. Additionally, we reported that the clinical outcome was characterized by a low oocyte maturation rate following ovum pick up and high multiple pronuclear formation rate after fertilization. However, the post-implantation course of embryos with ACA-positive cases has not yet been reported. Therefore, in this study, we analyzed the pregnancy and miscarriage rates in ACA-positive patients treated with Assisted Reproductive Technologies (ART). Study design, size, duration 6581 patients who underwent embryo transfer after antinuclear antibody testing between January 2014 and February 2020 were included in the analysis. Participants/materials, setting, methods The subjects were classified into three groups: ANA-negative (without ACA or any other ANA), ACA-positive (with only ACA) and ANA-positive (with ANA but not ACA). The cycle in which the gestational sac was confirmed was considered a positive pregnancy. The pregnancy and miscarriage rates were compared among the groups using “Ryan Test” for statistical analysis. Main results and the role of chance Of the 6581 eligible cases, the incidence of antinuclear antibody were 71.3% (4695/6581; ANA-negative), 0.9% (61/6581; ACA-positive) and 27.7% (1825/6581; ANA-positive). The pregnancy rates based on the total number of embryo transfer cycles for each were ANA-negative: 31.5% (5283/16792), ACA-positive: 17.6% (41/233), and ANA-positive: 32.4% (1891/5833). The pregnancy rates were significantly lower in the ACA-positive group than in the other groups. The miscarriage rate was 29.4% (1553/5283) in ANA-negative, 31.7% (13/41) in ACA-positive, and 28.0% (529/1891) in ANA-positive, with no significant difference between the three groups. Limitations, reasons for caution Retrospective analysis Wider implications of the findings: ACA-positive patients may benefit from a treatment strategy to increase the absolute number of oocytes by obtained in order to increase the chances of normal fertilization and attainment of implantation. Trial registration number none

Characterization of anti-nuclear antibodies in patients with oral submucous fibrosis and its clinicopathologic implications - An immunofluorescence study.

Background:Oral submucous fibrosis (OSF), widespread in the Indian subcontinent, is a chronic debilitating disease of the oral cavity having a high potential for malignancy. The etiology of OSF is debatable. However, recently, autoimmunity had been suggested to play a significant role in its etiology, yet unproven. Hence, this study was conducted to explore the presence of antinuclear antibodies (ANAs) in the serum of OSF patients which is one of the serum markers of autoimmune diseases and its possible clinicopathologic associations.Materials and Methods:A total of 105 blood samples were collected from patients with OSF (n = 45), age- and sex-matched healthy controls with (n = 30) and without (n = 30) areca nut chewing habit. Serum positivity of ANA was determined by immunofluorescence and correlated with the oral habits and severity of the disease measured by maximum mouth opening (MMO) and site of involvement.Results:Significantly higher incidence of ANA (35.6%) was found in 45 OSF patients than in the healthy group (P = 0.001). Prevalence of ANA positivity was found higher in females (n = 11; 68%) than males (P < 0.001). A significantly lower MMO (P = 0.00) was found in ANA positive patients (17 ± 6.21 mm) in contrast to MMO in ANA-negative patients (28.74 ± 6.58 mm). The mean duration of habit and frequency of habit between ANA positive and negative patients was not significant. A significantly more number of sites of involvement was seen in ANA positive cases (P = 0.004). Out of 16 ANA positive OSF cases, 10 cases showed + 2 and 6 cases showed + 3 fluorescence intensity. Speckled (n = 8), homogeneous (n = 5) and nucleolar pattern (n = 3) were the fluorescence patterns observed.Conclusion:The presence of autoantibodies such as ANA, female predilection, alteration of humoral and cellular immunity justifies OSF as an autoimmune disease. This study provides broader prospective to adopt therapies that selectively target autoimmune pathways.

Alpha-melanocyte stimulating hormone ameliorates disease activity in an induced murine lupus-like model

Alpha-melanocyte stimulating hormone (α-MSH) is a neuropeptide exhibiting anti-inflammatory activity in experimental models of autoimmune diseases. However, no studies thus far have examined the effects of α-MSH on systemic lupus erythematosus (SLE). This study aimed to determine the effects of an α-MSH agonist in induced murine lupus. Here we employed female Balb/cAn mice in which lupus was induced by pristane. Groups of lupus animals were treated daily with the α-MSH analogue [Nle4, DPhe7]-α-MSH (NDP-MSH) (1·25 mg/kg) injected intraperitoneally or saline for 180 days. Normal animals comprised the control group. Arthritis incidence, plasma immunoglobulin (Ig)G isotypes, anti-nuclear antibodies (ANA) and plasma cytokines were evaluated. Renal function was assessed by proteinuria and histopathological lesion. Glomerular levels of IgG, α-smooth muscle actin (α-SMA), inducible nitric oxide synthase (iNOS), C3, CD3, melanocortin receptors (MCR)1, corticotrophin-releasing factor (CRF) and α-MSH was estimated by immunohistochemistry. When compared with normal controls, lupus animals exhibited increased arthritis, IgG levels, ANA, interleukin (IL)-6, IL-10, proteinuria and mesangial cell proliferation together with glomerular expression of α-SMA and iNOS. Glomerular expression of MCR1 was reduced in lupus animals. NDP-MSH treatment reduced arthritis scores by 70% and also diminished IgG1 and IgG2a levels and ANA incidence. In the glomerulus, NDP-MSH treatment reduced cellularity by 50% together with reducing IgG deposits, and expression levels of α-SMA, iNOS and CRF were also all decreased. Taken together, our results suggest for the first time that α-MSH treatment improves several parameters of SLE disease activity in mice, and indicate that this hormone is an interesting potential future treatment option.

Evaluation of anti-nuclear antibodies and kidney pathology in Lewis rats following exposure to Libby amphibole asbestos

The prevalence of anti-nuclear antibodies (ANA) and self-reported systemic autoimmune diseases were increased in residents of Libby, MT, as was the incidence of ANA in Lewis rats exposed to Libby amphibole (LA) asbestos. However, rats induced to develop rheumatoid arthritis (RA) did not develop autoantibodies associated with RA, nor was RA exacerbated by LA exposure, suggesting that increased ANA expression might be related to some other autoimmune process. Libby residents self-reported increased numbers of physician-diagnosed cases of systemic lupus erythematosus (SLE). Thus, the goal of this study was to determine if the increased incidence of ANA in Lewis rats exposed to LA is related to the development of SLE-like disease. Female Lewis rats were intratracheally instilled bi-weekly for 13 weeks with total doses of 0.15, 0.5, 1.5, or 5.0 mg of LA or 0.5 or 1.5 mg of a positive control fiber, amosite. ANA incidence was significantly increased in all asbestos dose groups, although no dose response was observed. The occurrence of proteinuria was increased in LA 0.5, LA 5.0, and amosite 0.5 dose groups; however, the microscopic appearance of the kidneys was normal, no binding of autoimmune complexes to glomerular surfaces was observed, and antibodies to double-stranded DNA were not elevated. Therefore, an increased prevalence of ANA in rats exposed to asbestos does not appear to correlate with disease markers typically observed in SLE. Analysis of ANA specificity for extractable nuclear antigens (ENA) determined that 98% of ENA+ samples were specific for the Jo-1 antigen. Autoantibodies to Jo-1 have been reported in patients with interstitial lung disease, suggesting that autoantibodies to Jo-1 may be a biomarker for asbestos-related pulmonary disease.

Influence on Spontaneous Tissue Inflammation by the Major Histocompatibility Complex Region in the Nonobese Diabetic Mouse

We investigated the role of the major histocompatibility complex (MHC) region in the specificity of autoimmunity by analysing specifically the development of sialadenitis, but also insulitis, nephritis and autoantibody production in autoimmune-prone nonobese diabetic (NOD) mice where the MHC H2g7 haplotype had been exchanged for the H2q (NOD.Q) or H2p (NOD.P) haplotype. The exchange of H2 haplotype did not affect the frequency of sialadenitis because the H2q and H2p congenic NOD strains developed sialadenitis with the same incidence as NOD. However, the severity of sialadenitis varied among the strains, as NOD.Q >NOD >NOD.P. At 11-13 weeks of age, the NOD.Q (H2q) female mice developed more severe sialadenitis compared to NOD.P (H2p) (P=0.038). At 20 weeks, the NOD (H2g7) female mice showed more severe sialadenitis than NOD.P (P=0.049). This is in contrast to the development of insulitis in the present strains, because the incidence of insulitis was almost completely inhibited by the replacement of the H2g7 haplotype of NOD. The incidence of insulitis in NOD.Q was 11-22%, compared to 75% in NOD, which correlated well with lower titres of anti-glutamic acid decarboxylase (anti-GAD) antibodies in NOD.Q compared to NOD (P=0.009). However, the introduction of the H2q haplotype into the NOD strain instead directed the autoimmune response towards the production of lupus types of autoantibodies, because the incidence of antinuclear antibodies (ANA) in NOD.Q was 89% compared with 11% in NOD.P and 12% in NOD mice, which in turn correlated with a high incidence of nephritis in NOD.Q compared to NOD. Consequently, we show that different haplotypes of MHC are instrumental in directing the specificity of the spontaneous autoimmune inflammation.

Mitral valve prolapse in autoimmune thyroid disease: an index of systemic autoimmunity?

A coexistence of mitral valve prolapse (MVP) with autoimmune thyroid disease (AITD) has been described, but there are not sufficient data to explain this association. The aim of the present study was to investigate the prevalence of MVP in patients with AITD and to evaluate whether any correlation between MVP and certain immunological parameters exists. M-mode, two-dimensional Doppler echocardiography was performed in 29 patients with Graves' disease (GD), 35 with Hashimoto's thyroiditis (HT), 20 with nonautoimmune goiter, and 30 normal controls. Serum samples were examined for antinuclear antibodies (ANA), antibodies against extractable nuclear antigen (ENA), antiphospholipid antibodies (aCL), rheumatoid factor (RF), thyroid autoantibodies (TAAb), immunoglobulins and C3, C4. Eight of 29 GD patients and 8 of 35 HT patients had MVP, while none of the control group and 2 of 20 of the simple goiter group had MVP (p < 0.05). ANA were detected at low titers in 5 of 8 in MVP(+) GD versus 3 of 21 in MVP(-) GD (p < 0.05). In the HT group the MVP(+) patients had a significantly higher incidence of ANA and ENA, 5 of 8 and 2 of 8 versus 5 of 27 and 0 of 27 of MVP(-) patients, respectively, p < 0.05. A statistically significant higher incidence of aCL was found in HT MVP(+) patients. (3/8) versus HT MVP(-) 1/27, p < 0.05. RF levels (immunoglobulin A [IgA]) were significantly higher in MVP(+) patients. The association of MVP with nonorgan-specific autoantibodies indicates that MVP may also be an autoimmune disease. It is possible that patients with AITD who also have MVP may be at an increased risk to develop systemic autoimmunity.

Autoantibodies to phospholipids and nuclear antigens in non-pregnant and pregnant Colombian women with recurrent spontaneous abortions

Autoantibodies to negatively charged phospholipids have been reported to be associated with thrombotic events, thrombocytopenia and adverse pregnancy outcome, such as intrauterine growth retardation and recurrent spontaneous abortions (RSAs). In this study, autoantibodies to 6 phospholipid antigens and antinuclear antibody (ANA) were tested in Colombian women with a history of RSAs. Sixty-eight non-pregnant and 25 pregnant women with a history of RSAs comprised the study group. Twenty-five non-pregnant normal healthy women and thirty-one normal pregnant women served as controls. The non-pregnant women with RSAs showed a higher incidence of autoantibodies to cardiolipin (23% positive) as compared with non-pregnant normal controls (0% positive; P < 0.005). The incidence of autoantibodies to cardiolipin (28%; P < 0.005), phosphatidylethanolamine (16%; P < 0.005), phosphatidylserine (16%; P < 0.05), phosphatidylglycerol (16%; P < 0.05), phosphatidic acid (16%; P < 0.01) and phosphatidylinositol (20%; P < 0.01), in the pregnant women with RSAs was significantly higher than that of normal pregnant controls. There was no difference in the incidence of ANA in either group. In conclusion, women with a history of RSAs have a higher incidence of autoantibodies to phospholipids when compared to pregnant and normal controls. Autoimmune serological work-up is indicated during pregnancy in women with a history of RSAs.

Lupus-like autoimmune disease induced by interferon therapy for myeloproliferative disorders

Symptoms of autoimmune disease were evaluated in 125 patients with chronic myelogenous leukemia (CML) and in 12 patients with essential thrombocythemia undergoing treatment with recombinant interferon (IFN)-α-2b plus/minus low-dose recombinant IFN-γ. Twenty-seven of 137 patients (20%) developed rheumatoid symptoms. Furthermore, the incidence of antinuclear antibody (ANA) formation was studied. Elevated ANA titers were found in 5 19 (26%) of CML patients at the time of diagnosis and in 3 18 (17%) of patients treated with hydroxyurea or busulfan. During IFN treatment, 18 of 25 tested patients (72%) had elevated ANA titers. In 15 of these ANA-positive patients, clinical signs of autoimmune disease appeared. All these patients were under long-term IFN treatment and were in remission of disease. In three patients criteria for systemic lupus erythematosus were fulfilled. Severity of side effects has led to the discontinuation of IFN treatment in these patients. The data indicate that IFN-α and IFN-γ can induce ANA associated with autoimmune disease in patients with myeloproliferative disorders.

Autoimmune Phenomena in Patients with Malignant Carcinoid Tumors During Interferon-α Treatment

Several previous reports suggest an association between treatment of patients with interferon-alpha (IFN-alpha) and development of autoantibodies and autoimmune disease. We here summarize the experience from a group of 135 patients with midgut carcinoid tumors treated with natural leukocyte IFN-alpha or recombinant IFN-alpha (rIFN-alpha). An unusual high incidence of antimicrosomal antibodies (MsAb) or anti-thyroglobulin antibodies (TgAb) and thyroid disease manifested as hyperthyroidism, hypothyroidism or a biphasic Hashimoto-like disease was seen, with female predominance. The incidence of antinuclear antibodies (ANA) was also increased, but equally in both sexes. Antibodies to parietal cells were found in 5 cases and 4 patients with pernicious anemia were detected. Two patients developed vasculitis of leukocytoclastic type and one a syndrome resembling systemic lupus erythematosus. Some patients treated with rIFN-alpha develop anti-IFN antibodies. Such antibodies may also be autoantibodies reacting with autologous IFN-alpha. They can neutralize the biologic activity of administrated IFN preparation and cause therapeutic failure. The implications of the various autoimmune manifestations during IFN-alpha treatment are discussed.

Low incidence of antinuclear antibodies in dermatomyositis with malignancy.

Low incidence of antinuclear antibodies in dermatomyositis with malignancy.

Factors related to the presence of autoantibodies in patients with chronic mental disorders

Serum samples from 307 patients with various chronic mental disorders were examined for the presence of several autoantibodies. Autoantibodies detected included antinuclear antibodies (ANA) in 122 307 (39.7%), rheumatoid factor (RF) in 23 307 (7.5%), anticardiolipin antibodies (anti-CL) in 23 304 (7.6%, IgM in 12 patients, IgM in 13 patients). Isolated cases with IgG anti-dsDNA, anti-Ro(SSA), and anti-Ro(SSA)/anti-La(SSB) were also identified. The analysis of data revealed that the aging process in patients studied contributed significantly to the incidence of ANA (p < 0.0001) and RF (p < 0.01). In addition, the chronic administration of chlorpromazine (CPZ) was associated with the presence of ANA (p < 0.03) as well as with the presence of IgM and/or IgG anti-CL antibodies (p < 0.003). Finally, the diagnosis of schizophrenia correlated with the presence of ANA (p < 0.001). This study represents the autoantibody profile of patients with chronic mental disorders and emphasizes the multifactorial origin of autoantibody response in psychiatric patients.

Antinuclear antibodies in the sera of patients with nasopharyngeal carcinoma

We studied the production of heterophile antinuclear antibodies (ANAs) in the sera of 50 patients, 20 with nasopharyngeal carcinoma (NPC) and 30 with other head and neck cancers (laryngeal cancer and maxillary cancer), before and after radiation therapy. A higher incidence of ANAs was found in the sera of patients with NPC and ANA production in these patients was higher after radiation therapy. We therefore performed in vitro experiments to explore the mechanisms of ANA production in the serum of postirradiated NPC patients. X-ray-irradiated NPC-derived cells (NPC-KT) produced a large amount of Epstein-Barr virus (NPC EBV) compared with non-irradiated NPC-KT cells. Nasopharyngeal carcinoma EBV-infected lymphocytes produced high levels of ANAs. These data suggest that lymphocytes infected by EBV from NPC cells may produce ANAs in the sera of NPC patients.

Change of incidence of antinuclear antibodies in serum of NOD mouse with aging

Extractable nuclear antigens (ENA) were prepared from liver of C57BL/6J mouse and analyzed by SDS PAGE Western-immunoblotting techniques. Some protein components of the ENA, with molecular weights of 94 K, 65 K, 32 K, and 26 K, reacted with antinuclear antibodies in the sera of NOD mice. Incidence of antinuclear antibodies in the sera of NOD mice with aging were measured by ELISA method using the ENA as antigen. The antinuclear antibodies were not detected in young NOD mice (10 weeks old). However, the incidence increased with aging and reached 100% in the female NOD mice of 40 weeks. In the male NOD mice, the incidence of antinuclear antibodies was delayed and low in comparison with that in female.

Ｓｊｏｅｇｒｅｎ症候群における唾液腺造影像と免疫学的検査所見との関連

42 patients, suspected as having Sjogren's syndrome (88) based on sialogram of the parotid gland and were diagnosed as not having other autoimmune diseases, were evaluated in order to clarify the relationship of the sialographical appearance to immunological findings of SS.According to Fukuda's sialographical classification for SS (Class I-Class IV), tin patients were classified into three groups. 21 patients were classified as Class II, which suggests an early stage of SS. 8 patients were classified into Class III and 13 into Class IV. which suggest advanced stages for SS. Class I was not observed in this group of patients. Numbers of both peripheral blood leukocytes (leu) and lymphocytes (lym) of Class 17 patients (leu: 4, 200/mm3, lym: 1, 400/mm3) were significantly lower than those of Class II patients (leu: 5, 900/mm3, lym: 1, 900/mm3). Increase in γ-globulin, IgA, IgG and IgM in the sera of the patients was also observed as the sialographical classification advanced. Serum anti-nuclear antibody (ANA) and rheumatoid factor (RF) were observed in 43% and 38% of Class II patients, 63% and 50% of Class III patients, and 67% and 75% of Class IV patients, respectively. A high incidence of ANA and RF were observed also in Class II patients, and increases in the incidence of the above factors were seen as the sialographical classification advanced. Serum anti-SS-A antibody and anti-SS-B antibody were demonstrated in 57% and 29% of Class III patients, and 88% and 38% of Class IV patients. In contrast, the above antibodies were not observed in the sera of Class II patients.

Antinuclear antibodies in the relatives and spouses of patients with systemic sclerosis.

The families of 65 patients with systemic sclerosis were examined clinically and serum samples from each subject were tested for antinuclear antibodies (ANA) by immunofluorescence on HEp2 cells and for precipitating antibodies to soluble cellular antigens including Scl-70. Of 217 blood relatives, 58 (27%) had ANA (42 speckled, 13 nucleolar, one centromere, two homogeneous); 22 (10%) had precipitins, one anti-Scl-70, one anti-PM-Scl, one anti-nRNP, two anti-Ro(SSA), the remainder unidentified). Family members tended to share ANA patterns. Of 38 spouses, nine (24%) had ANA (all speckled) and two showed unidentified precipitins. This compares with an incidence of ANA and precipitins in a control population of 8% and 1% respectively. Antibodies were more common in female than male relatives (particularly in mothers and sisters of probands). Twenty one of the 58 family members with ANA had clinical features of connective tissue disease; the remainder were asymptomatic. The presence of genetic factors influencing autoimmunity is suggested by the incidence of autoantibodies in first degree relatives. Similar observations in spouses, however, indicate that environmental factors may also have a role in these immune abnormalities.

Association of HLA and autoantibody in transfused sickle cell disease patients.

This study evaluates autoantibody production in sickle cell disease patients and determines whether genes in the major histocompatibility complex are associated with autoantibody responses. Rheumatoid factor was significantly increased for both male and female patients and was less prevalent in highly transfused patients. Significant increases were also detected in the incidences of antinuclear antibody for females and antismooth muscle antibody for males. Low incidence of antinuclear antibody was significantly associated with HLA-DR3. Significant associations were also found between the incidence of antinuclear antibody and both HLA-A28 and B15.

Rheumatoid factors in the sera of patient with gastrointestinal carcinoma.

One hundred and nineteen patients with gastrointestinal (GI) malignancy (80 colorectal, 25 gastric and 14 pancreatic carcinoma) were studied for rheumatoid factors (RF), antinuclear antibodies (ANA) and immunoglobulin levels and the findings correlated with size of tumor, stage of disease and survival. Twenty three (19.3%) of the patients were RF seropositive compared to 5.7% of 70 matched controls (P = 0.02). In two thirds of the seropositive patients RF were detected prior to the initiation of treatment. The proportion of RF seropositivity increased significantly in patients with tumors larger than 4 cm and in patients with Stage D disease. The authors found a high incidence of ANA in the patients: 32.4% compared to 8% in normal subjects (P less than 0.01), but the proportion of RF in this group was not significantly different. Survival distributions of the RF positive cases were different from that of the other patients (18 versus 25 months median survival); however, this was not statistically significant. These findings indicate that RF in GI cancer patients sera is not rare and can be related mainly to "tumor load," although not considerably affecting survival.

Antinuclear antibodies in childhood diabetics.

Antinuclear antibodies (ANA) were detected both in type 1 diabetic children and in control subjects. The incidence of ANA in eighty of these diabetics was 16.3%, as determined using two different substrates, human pancreas and human peripheral leucocytes. The incidence and the patterns in the detection of ANA were the same. Four hundred and seventy-three children and one thousand one hundred and twenty-five adults served as the controls. The incidence of ANA in non-diabetic children was 0.8% and that in one adult population was 1.1%. Therefore, the incidence of ANA in childhood diabetics was significantly higher. We studied autoantibodies in childhood diabetics, in normal children and in one adult population. Pancreatic islet cell antibodies (ICA) were detected in 29 out of 80 type 1 diabetics (36.3%) in two out of 473 normal children (0.4%) and in six cases in one population (0.5%). thyroid microsomal antibodies (MCHA) were detected in 9 out of 80 childhood diabetics and the incidence of MCHA in type 1 diabetics was significantly higher than in the controls.

Beta-adrenergic-receptor blockers and antinuclear antibodies in hypertension.

It has recently been reported that the Beta-adrenergic receptor-blocker acebutolol accelerates the development of antinuclear antibodies (ANAs) in hypertensive patients. We examined data from over 1500 hypertensive patients to determine whether this effect is associated with other beta blockers. Groups of patients treated with acebutolol, atenolol, labetalol, and pindolol all displayed increased development of ANAs relative to patients on other medication. When patients taking methyldopa (a drug associated with a high ANA incidence) were excluded from the analysis, only acebutolol retained an association (P less than 0.001) with ANA production. Sequential studies to assess the development of ANAs in patients during the course of beta-blocker treatment revealed a similar pattern. With methyldopa patients excluded, the fraction of patients developing ANAs was less then 10% for all but atenolol (10.9%), labetalol (13.8%), and acebutolol (33%). Thus, although some of the beta blockers may be associated with an increase in ANA incidence, the dramatic effects of acebutolol do not appear to be a group property.