Clinical Significance Of Antinuclear Antibodies Research Articles

Clinical significance of antinuclear antibodies in primary immune thrombocytopenia.

There are discrepancies across guidelines about whether the dosage of antinuclear antibodies (ANAs) is of use at the diagnosis of primary immune thrombocytopenia (ITP). This review describes the current knowledge about ANA prevalence in patients with primary ITP, and their potential usefulness as biomarkers for ITP evolution, response to treatments and increased risk of subsequent development of systemic lupus and thrombosis.

Differences in the Clinical Significance of Antinuclear Antibodies According to Titers and Patterns in Children.

This study aimed to evaluate the differences in the clinical significance of antinuclear antibody (ANA) according to their titers and patterns in the diagnosis of systemic autoimmune diseases (AiD) in pediatric patients. Of the 2442 children who had undergone an ANA test, 473 (19.4%) were positive for ANA, of whom 33 (7.0%) were diagnosed with significant AiD. The positive predictive value (PPV) for significant AiD was considerably high on application of an ANA titer of ≥1:640, and the PPV of a dense fine speckled (DFS) pattern was significantly lower compared with those of speckled and homogenous patterns. The diagnostic value of ANA positivity for AiD is limited, and the clinical significance of the DFS pattern is relatively lower compared with that of other patterns, such as homogenous and speckled patterns, in children. It is necessary to approach the significance of ANA in children individually depending on titers and patterns.

The clinical significance of antinuclear antibodies and specific autoantibodies in juvenile and adult systemic lupus erythematosus patients.

Juvenile systemic lupus erythematosus (JSLE) and adult SLE (ASLE) patients present with different clinical manifestations, but it is unknown if there are differences in their antinuclear autoantibody (ANA) profiles or if staining patterns are associated with specific autoantibodies and clinical manifestations. To determine whether distinct types and numbers of ANA-staining patterns are associated with specific autoantibodies and clinical manifestations in JSLE and ASLE patients. A retrospective study was performed in Thai children (n = 146) and adults (n = 180) diagnosed with SLE using the Systemic Lupus International Collaborating Clinics classification criteria. JSLE patients with a homogeneous pattern of staining and anti-dsDNA or anti-nucleosome antibodies in serum, developed renal involvement, leukopenia and acute/subacute cutaneous LE. Coarse speckled pattern with anti-RNP or anti-Sm showed thrombocytopenia and renal involvement in JSLE patients, but leukopenia in both groups. JSLE patients with fine-coarse speckled pattern and anti-RNP, anti-Sm, anti-Ro-52 or anti-SSA developed leukopenia, thrombocytopenia and renal involvement, whilst hemolytic anemia and serositis were commonly found in those with anti-Ro-52. Median SLEDAI score was higher in JSLE than ASLE patients. Detailed ANA-staining patterns with specific autoantibodies show particular clinical manifestations and hence prompt further clinical investigations in both JSLE and ASLE patients. Therefore, this study demonstrates that distinct patterns of ANA staining and specific autoantibodies are clinically important in both children and adults with SLE.

Clinical significance of antinuclear antibodies associated with the nuclear dense fine speckled immunofluorescence pattern in autoimmune disease

Objective To explore the prevalence of the nuclear dense fine speckled (DFS) immunofluorescence pattern in routine antinuclear antibodies (ANA) testing and its significance in patients with autoimmune diseases (AID). Methods The ANA in 13 728 specimens were measured by indirect immunofluorescence (IIF) using HEp–2 cell slides from department of clinical laboratory, wenling hospital from 2011 to 2014. The frequencies, clinical manifestations and laboratory features of DFS positivity were restrospectively analyzed in patients with AID, using χ2 test. Results ANA was positive in 20.56%(2 822/13 728) of the total patients, and the frequency of DFS pattern was observed in 1.81%(248/13 728) of the total patients and in 8.79%(248/2 822) of the patients with ANA positivity. In different age groups (≤20 years old, 21–49 years old and ≥50 years old), there were statistical significance of DFS pattern positive rate (male: χ2=18.17, P<0.01; female: χ2=1 500.00, P<0.01). And the highest frequency of ANA positivity was observed in patients from department of rheumatology (30.07%). The frequency of DFS pattern was higher in the departments of infection (32.58%), dermatology (21.76%), neurology (18.58%) and nephrology (6.73%) among the patients with ANA positivity (χ2=123.00, P<0.01). Amony the 248 cases with DFS pattern positivity.41 cases were AID (16.53%) and 207 cases were non– autoimmune diseases (83.47%). In AID group 13 cases were autoimmune thyroiditis (31.71%), 12 cases were rheumatoid arthritis (29.27%), 4 cases were autoimmune liver disease (9.76%), 4 cases were undifferentiated connective tissue disease (9.76%), 3 cases were ankylosing spondylitis (7.32%), 2 cases were Sjogren's disease (4.88%), 2 cases were inflammatory bowel disease (4.88%) and 1 case was systemic lupus erythematosus (2.44%). The titers of DFS in patients with AID were predominantly above 1∶320 and less than 1∶100 in non–AID. AID patients with DFS pattern positivity have different clinical manifestations and laboratory features. Howerer, antinuclear antibodies (ANAs) in 15 specific auto–antibodies were all negative. Conclusions The DFS pattern is a common pattern in ANA positivity patients and it mainly exists in non–AID patients. Further more, it is suggested that patients with DFS pattern identified by IIF should then be tested for anti–DFS70 antibodies with a specific immunoassay. (Chin J Lab Med, 2015, 38: 173–177) Key words: Autoimmune disease; Antibodies, antinuclear; Fluorescent antibody technique, indirect

Autoimmune thyroid diseases and nonorgan‑specific autoimmunity

Autoimmune thyroid diseases (ATD), as the most common organ‑specific autoimmune disorder, is frequently accompanied by other organ- and nonorgan‑specific autoimmune diseases. Although the exact pathogenic mechanism of the coexistence of autoimmune disorders has not been clearly defined, genetic and environmental factors, immune defects, and hormonal changes, may play a key role in polyautoimmunity. The role of human leukocyte antigen (HLA) haplotypes, HLA-B8 and -DR3, in the overlapping of autoimmune disorders was well supported by higher frequency of these haplotypes in primary Sjögren's syndrome (PSS) and ATD. In addition, polymorphisms of the cytotoxic T lymphocytic antigen 4 gene have been reported to be associated with many autoimmune disorders especially those coexisting with ATD. Definite noncasual association of ATD has been clearly documented in patients with PSS, rheumatoid arthritis, and systemic lupus erythematosus. Possible association with ATD is also considered in systemic sclerosis and dermatomyositis. Many authors documented a significantly higher prevalence of antinuclear antibodies (ANAs) in ATD patients in comparison with controls; however, the clinical significance of ANAs in this group is still unknown. The presence of other non‑organ‑specific antibodies has not been convincingly demonstrated. On the other hand, the prevalence of antithyroid antibodies as well as ATD is higher in patients with systemic connective tissue disease compared with the general population. Basedon these data, there is no evidence for the utility of ANA testing in patients with ATD, but because of the high prevalence of ATD and antithyroid autoantibodies, it is clinically important to screen patients with autoimmune rheumatic disorders for the presence of thyroid autoimmunity.

Antinuclear antibodies in recurrent idiopathic pericarditis: Prevalence and clinical significance

Background A positive result for antinuclear antibodies (ANA), often as a fortuitous observation, may be cause for concern in idiopathic recurrent pericarditis (IRP), nevertheless data are lacking on their prevalence and clinical significance. This study is sought to investigate the prevalence and clinical significance of ANA in IRP. Methods ANA titres were assessed in consecutive patients with recurrent pericarditis, and matched healthy controls. Baseline and follow-up data were recorded and compared according to ANA results. Results A total of 145 consecutive patients with recurrent pericarditis were studied: 122 patients with IRP, 23 patients with pericarditis due to known etiologies (rheumatologic diagnoses and postpericardiotomy syndrome), and 122 healthy controls. ANA were detected in 53 of 122 (43.4%) patients with IRP, and in only 12 of 122 (9.8%) controls ( p < 0.001). Low titres (1/40–1/80) were found in the majority of cases, while moderate positivity (1/160–1/320) was more common in patients with a known rheumatic disease (26.7% vs. 5.7%; p = 0.020). High concentrations of ANA (≥ 1/640) were not recorded. Women were at increased risk for ANA (OR 2.22 95%CI 1.07–4.60; p = 0.033). During a mean follow-up of 32 months, complications and new diagnoses were similar in patients with or without ANA positivity. Conclusions Low-positive titres are more common in patients with IRP than in controls, suggesting a possible autoimmune pathogenesis. Nevertheless, they are often a clinically non-specific finding. Routine serologic testing for ANA suggests a source for recurrent pericarditis in less than 10% of cases, and in these cases other evidence typically suggests the underlying disease.

Predictive role of anti‐gp210 and anticentromere antibodies in long‐term outcome of primary biliary cirrhosis

Because some of the autoreactive T-cell clones specific for human PDC-E2 cross-react to mimicry peptides having an EIExDK motif derived from nuclear antigens such as human gp210 and sp100, we studied the clinical significance of antinuclear antibodies (ANA) in primary biliary cirrhosis (PBC) patients registered to the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ). We found that there are two different types of progression in PBC; one is a hepatic failure-type progression which is represented by positive anti-gp210 antibodies and the other is a portalhypertension-type progression which is represented by positive anticentromere antibodies. We discuss the predictive role of these ANA in the long-term outcome of PBC and the mechanisms by which two different PBC progression types occur based on molecular mimicry and aberrant expression of nuclear antigens.

Experimental and Clinical Significance of Antinuclear Antibodies in Liver Transplantation

Histone H1 and high-mobility group box 1 (HMGB1) proteins are known to initiate an immune reaction, and the corresponding antibodies (Abs) possess immunosuppressive activity. In the present study, we aimed to evaluate the immunological role of antinuclear Abs in experimental and clinical liver transplantation. In a rat tolerogenic orthotopic liver transplantation (OLT) model, antihistone H1 and HMGB1 titers were induced during the rejection and tolerance induction phases, respectively. Those Ab responses also were confirmed in a drug-induced tolerance model (acute rejection model + cyclosporin A [0 to 14 days after OLT]). We also found a similar tendency in our clinical drug-free patient (who experienced complete cessation of any immunosuppressive treatments) and that antinuclear Abs induced in the serum after cessation of immunosuppressants play a part of immune privilege in this patient. These results suggest that antinuclear Abs are important factors for overcoming rejection and the subsequent tolerance induction in liver transplantation.

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

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

P-03 Prevalence, incidence and clinical significance of antinuclear antibodies in melanoma patients associated with adjuvant use of pegylated interferon-α2b

P-03 Prevalence, incidence and clinical significance of antinuclear antibodies in melanoma patients associated with adjuvant use of pegylated interferon-α2b

Clinical significance of antinuclear antibodies in systemic rheumatic diseases.

Autoantibodies directed to intracellular antigens can be detected in many systemic rheumatic diseases. In this review, we discuss the clinical significance of antinuclear antibodies (ANA) associated with systemic lupus erythematosus (SLE), Slögren's syndrome, scleroderma and polymyositis/dermatomyositis, the immunogenetic factors associated with these four autoimmune diseases, and the possible role of autoantibodies in the etiopathogenesis of autoimmune disease. The antibodies associated with systemic rheumatic diseases serve as important tools in the initial diagnosis, and they are also useful in the evaluation of prognosis. However, for correct conclusions, the autoantibody findings should be carefully considered and interpreted in clinical context.

Clinical Significance of Antinuclear Antibodies in Japanese Patients with Systemic Sclerosis

Clinical significance of specific antinuclear antibodies (ANA) in Japanese patients with systemic sclerosis was studied. The patients with systemic sclerosis were classified into four groups according to ANA: (1) anticentromere antibody-positive; (2) anti-Scl-70 antibody-positive; (3) anti-nRNP antibody-positive, and (4) others. The mean score (the number of positive signs in six selected specific signs) of the patients with anti-Scl-70 antibody was significantly higher than those of the other three groups. More frequent contracture of phalanges in the patients with anti-Scl-70 antibody, less diffuse pigmentation in the patients with anti-nRNP antibody, and less pulmonary fibrosis in the patients with anticentromere antibody were revealed. As shown above, the detection of specific ANA in systemic sclerosis is clinically important.

Clinical study of antinuclear antibody and its relation to clinical course.

ABSTRACTIndirect immunofluorescent test was used to study the clinical significance of antinuclear antibodies (ANA) in 116 systemic lupus erythematosus (SLE) patients. It was found that ANA was present in 96.5% of SLE patients and that their presence could serve as an important laboratory characteristics. A titer of 160 or more could also serve as suggestive evidence for SLE. The chief morphological appearance of ANA was peripheral pattern and homogenous pattern. The peripheral pattern was associated with high titer. A change of titer and pattern were interrelated. A change from homogenous to peripheral pattern indicated a downhill course of the disease, and a change from peripheral to homogenous pattern showed clinical improvement of the disease.

The clinical significance of antinuclear antibodies.

A number of different types of antinuclear antibodies have been characterized, and their clinical significance is beginning to become clear. The anti-DNA type correlates closely with renal injury and severity of clinical disease in systemic lupus erythematosus. Antiribonucleoprotein appears to be related to mixed connective tissue disease.