OBJECTIVEA study on the value of antimitochondrial antibody (AMA) and its subtypes anti-M2, anti-M4, and anti-M9 in diagnosing primary biliary cirrhosis (PBC).

METHODSAntimitochondrial antibody was detected by indirect immunofluorescence and anti-M2, anti-M4 and anti-M9 by Western blotting. AMA and anti-M2 of 78 PBC patients, of 35 non-PBC hepato-biliary disease patients and 20 healthy controls were studied and anti-M2, anti-M4 and anti-M9 were studied in 30 of the 78 PBC patients.

RESULTS96.2% (75/78) of PBC patients were AMA positive and 94.9% (74/78) of PBC patients were anti-M2 positive. Only three among the 35 non-PBC patients were positive for AMA (one with very low titre). None of the 35 non-PBC patients was anti-M2 positive. AMA and anti-M2 were negative in all the healthy controls. Among the 30 anti-M2 positive patients, 16 patients were anti-M4 positive (16/30, 53.3%) and 4 patients were anti-M9 positive (4/30, 13.3%).

CONCLUSIONAMA and its subtypes (special anti-M2) are important sero-immunological markers for the diagnosis of PBC.

Autoantibodies ; blood ; classification ; Female ; Humans ; Liver Cirrhosis, Biliary ; diagnosis ; immunology ; Male ; Mitochondria, Liver ; immunology

Latent autoimmune diabetes in adults (LADA), presenting with a similar phenotype of type 2 diabetes at early stage, belongs to the slowly progressive subtype of autoimmune type 1 diabetes. LADA differs from classic juvenile-onset type 1 diabetes in which its autoimmune destructive process of islet beta-cells is much slower, so LADA may serve as a human model of autoimmune type 1 diabetes. Although no international standardized criteria for the diagnosis of LADA has been established, it should be noted that LADA has some specific features in clinical characteristics, susceptible genotypes, cellular and humoral immune markers, as well as islet pathology. Presence of islet autoantibodies is necessary for the diagnosis of LADA. Early insulin intervention may preserve residual islet beta-cell function in LADA. The different pathological manifestations of LADA with different autoantibody titers can help throw light on the autoimmune process, laying foundation of prevention or even cure of type 1 diabetes.
Adult ; Autoantibodies ; blood ; Diabetes Mellitus, Type 1 ; classification ; diagnosis ; drug therapy ; Humans ; Insulin ; therapeutic use ; Islets of Langerhans ; immunology

OBJECTIVE: To explore the role of IL-21 in the pathogenesis of myasthenia gravis (MG) and its influence on the the class switch of anti-AChR antibodies. METHODS: Blood was taken from 26 patients and 18 healthy controls, and the expression of IL-21R mRNA in peripheral blood mononuclear cells (PBMCs) was detected by RT-PCR. The expression of IL-21R on B lymphocytes was measured by flow cytometry, while the concentrations of serum IL-21 and the levels of anti-AChR-IgG and its isotype IgG(1), IgG(2), and IgG(3) were tested by ELISA. RESULTS: The serum concentration of IL-21 in the MG group was higher than that in the control group (31.686±8.499 pg/mL, 15.147±6.366 pg/mL) and the difference was significant (P<0.01). IL-21R mRNA expressed on PBMCs in the MG group was higher than that in the control group (0.139±0.052, 0.101±0.022), and the difference was significant (P<0.05). There was no difference between ocular MG and generalized MG subgroup (P>0.05). Compared with the control group, the expression of IL-21R on B lymphocytes also increased in the MG group (P<0.05). In the anti-AChR-Ab positive MG group, the serum concentration of IL-21 showed positive correlation with anti-AChR-IgG(P<0.05),but no correlation with its isotype IgG(1), IgG(2), and IgG(3), respectively(P>0.05). Expression of IL-21R mRNA in the PBMCs showed no correlation with the level of serum anti-AChR-IgG and its isotype IgG(1), IgG(2), and IgG(3), respectively(P>0.05); however the expression of IL-21R in B lymphocytes showed positive correlation with anti-AChR-IgG and it's isotype IgG(1) and IgG(3) (P<0.05,P<0.01,P<0.05), but no correlation with IgG(2) (P>0.05). CONCLUSION IL-21 might induce the class switch of anti-AChR antibodies to IgG(1) and IgG(3) isotype through IL-21R on B lymphocytes which promotes the pathogenesis of the MG.
Adolescent ; Adult ; Autoantibodies ; classification ; immunology ; Female ; Humans ; Immunoglobulin Class Switching ; immunology ; Immunoglobulin G ; classification ; Interleukins ; blood ; genetics ; Male ; Middle Aged ; Myasthenia Gravis ; blood ; immunology ; RNA, Messenger ; blood ; genetics ; Receptors, Cholinergic ; immunology ; Receptors, Interleukin-21 ; blood ; genetics ; Young Adult

INTRODUCTIONWith advancement in the understanding of the pathogenesis underlying diabetes mellitus (DM), the boundary between type 1 and type 2 DM (T1DM and T2DM) does not seem to be as clear cut as previously thought. This study was designed to test the possibility of overlap between the spectra of immune-mediated DM and insulin resistance.

METHODSTo test for the possibility of overlap, we looked for autoantibodies typical of T1DM in patients with classical T2DM, and insulin resistance in patients with T1DM. Autoantibodies against islet cell antigen, glutamic acid decarboxylase-65 and insulinoma-associated antigen-2 were tested in 82 patients with T2DM and 27 patients with T1DM. The patients had been diagnosed on clinical criteria using standard laboratory techniques. Clinical parameters of diagnostic importance were noted, and homeostatic model assessment of insulin resistance (HOMA-IR) was calculated using fasting insulin and fasting blood glucose ratio.

RESULTSAutoantibodies against one or more beta cell antigens were detected in 12.19% of patients clinically diagnosed to have T2DM, and insulin resistance (HOMA-IR > 2.5) was diagnosed in 37.03% of patients with T1DM. It was not possible to identify any combination of clinical or biochemical markers that could predict autoantibody positivity in T2DM patients. T1DM patients with insulin resistance had a significantly higher body mass index than their insulin-sensitive counterparts (p = 0.02).

CONCLUSIONAutoantibodies against beta cell antigens are detectable in insulin-resistant T2DM patients, and insulin resistance may be present in relatively overweight T1DM patients. No differentiating clinical features that might predict autoantibody positivity in T2DM patients were found.

Adolescent ; Adult ; Autoantibodies ; blood ; immunology ; Biomarkers ; blood ; Blood Glucose ; analysis ; Body Mass Index ; Cross-Sectional Studies ; Diabetes Mellitus, Type 1 ; classification ; immunology ; Diabetes Mellitus, Type 2 ; classification ; immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Insulin Resistance ; immunology ; Male

PURPOSE: A possible involvement of autoimmune mechanism in the pathogenesis of bronchial asthma has been proposed. Recently, alpha-enolase protein was identified as a major autoantigen recognized by circulating IgG autoantibodies in patients with severe asthma. To evaluate a possible pathogenetic significance of these autoantibodies in severe asthma, isotype (IgG, IgA, IgM, and IgE) and IgG subclass (IgG1, IgG2, IgG3, and IgG4) distributions of autoantibodies to recombinant human alpha-enolase protein were analyzed. PATIENTS AND METHODS: We examined serum samples from 10 patients with severe asthma and 7 patients with mild-to-moderate asthma, and 5 healthy controls by immunoblot analysis. Severe asthma was defined as patients having at least 1 severe asthmatic exacerbation requiring an emergency department visit or admission in the last year despite continuous typical therapies. RESULTS: IgG1 was the predominant IgG subclass antibody response to alpha-enolase protein in patients with severe asthma. IgG1 autoantibody to alpha-enolase protein was detected in 7 of 10 patients with severe asthma (70%), 1 of 7 patients with mild-to-moderate asthma (14.3%), and none of 5 healthy controls (0%) (chi-square test; p < 0.05). IgA, IgM, and IgE autoantibodies to alpha-enolase protein could not be detected in patients with severe asthma. CONCLUSION: IgG1 subclass was the predominant type of autoantibody response to alpha-enolase protein in patients with severe asthma, suggests a possibility of IgG1 autoantibody- mediated complement activation in the pathogenesis of severe asthma.
Adult ; Aged ; Asthma/*enzymology/*immunology ; Autoantibodies/*blood/classification ; Autoantigens ; Case-Control Studies ; Complement Activation ; Female ; Humans ; Immunoglobulin G/blood/classification ; Immunoglobulin Isotypes/blood ; Male ; Middle Aged ; Phosphopyruvate Hydratase/*immunology ; Recombinant Proteins/immunology ; Young Adult

The data of 1,265 in-patients with diabetic ketosis or ketoacidosis treated in West China Hospital from October 2005 to October 2011 were analyzed retrospectively, and 8 of whom met fulminant type 1 diabetes (F1D) diagnostic criteria. The clinical features of the 8 F1D patients were investigated and compared with other 16 newly diagnosed autoimmune type 1 diabetes (T1D) patients, gender- and age-matched and with acute onset of ketoacidosis. During the six years between 2005 and 2011, the incidence of FID was 6.3 per thousand (8/T265) among all patients with diabetic ketosis or ketoacidosis admitted to the West China Hospital. The averaged age of the patients at onset of F1D was (30. 1 +/- 9. 7) years old, and the duration of diabetes was (4. 0 +/- 2. 4) days. Five of the 8 F1D patients had flu-like symptoms, and 7 had gastrointestinal symptoms. Blood glucose of F1D patients on admission was significantly higher than that of autoimmune T1D patients (P<0. 01), while the glycated hemoglobin (HbAlc) was lower than that of autoimmune T1D patients (P<0. 01). Additionally, fasting and postprandial C-peptide was significantly lower in F1D patients, with more severe acidosis, electrolytes and acid-base disturbances. The data suggest, that, compared with the autoimmune T1D patients, F1D patients have more complicated and more severe clinical manifestation with more severe hyperglycemia, more significant insulin deficiency and more obvious fluid electrolytes and acid-base disturbances. However, the sensitivity and the specificity of the diagnostic criteria of F1D are still needed to be improved for the Chinese people, so more multi-center and large-scale clinical trials should be conducted in the future.
Adult ; Autoantibodies ; blood ; China ; epidemiology ; Diabetes Mellitus, Type 1 ; classification ; diagnosis ; epidemiology ; Diabetic Ketoacidosis ; etiology ; Humans ; Hyperglycemia ; epidemiology ; immunology ; Incidence ; Retrospective Studies ; Young Adult

Using two-kidney one-clip renal hypertensive (2K1C group), stress-induced hypertensive (neural group), DOCA-salt treated hypertensive (DOCA group) and spontaneously hypertensive rats (SHR group), to investigate the change in AT(1A)-receptor autoantibodies (AT(1A)-AAs) during the development of the four types of hypertension. The biological activities of AT(1A)-AAs were examined. It was shown that the frequency of occurrence and titres of AT(1A)-AAs increased significantly during the development of hypertension. In the four hypertensive groups studied, the occurrence of AT(1A)-AAs was most prominent in SHR, 2K1C and neural groups. The biological effects of AT(1A)-AAs were shown to increase the beating frequency of cultured neonatal myocardial and vascular contractile tension. It is suggested that autoimmune mechanisms are involved the pathogenesis of different types of hypertension and the AT(1A)-AAs may be one of the mechanisms leading to cardiac hypertrophy.
Animals ; Autoantibodies ; blood ; Desoxycorticosterone ; administration & dosage ; Hypertension ; classification ; etiology ; immunology ; physiopathology ; Hypertension, Renovascular ; immunology ; physiopathology ; Male ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Rats, Wistar ; Receptor, Angiotensin, Type 1 ; immunology ; Stress, Physiological ; physiology

Rheumatoid arthritis (RA) is an autoimmune disease that results in a chronic inflammatory disorder, which principally attacks the small joints. Several autoantibodies, such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody, are known to be associated with RA. Anti-proliferating cell nuclear antigen (PCNA) antibodies are mainly observed in patients with systemic lupus erythematosus (SLE). Indeed, a high titer of these antibodies is considered highly suggestive of SLE; however, anti-PCNA antibodies also appear in other autoimmune diseases. Two previous reports described RA patients with low titers of anti-PCNA antibodies, respectively. In this report, we describe a case of an RA patient exhibiting a high titer (>1:2,560) of anti-PCNA antibodies. The 56-yr-old female patient, with no underlying disease or medication history, presented with multiple joint pain and morning stiffness that had begun 6 months prior. The erythrocyte sedimentation rate (ESR) and RF were elevated (102 mm/hr and 77 IU/mL, respectively), and C-reactive protein (CRP) was 0.8 mg/dL. While the test for anti-CCP antibodies was negative, an anti-PCNA pattern (>1:2,560) and a homogeneous pattern (1:320) were detected by autoimmune target (AIT) test. The presence of anti-PCNA antibodies was subsequently confirmed using the double immunodiffusion method. The anti-dsDNA test was also positive (1:160). X-ray imaging showed soft tissue swelling of multiple joints of both hands and wrists. According to the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria, the patient was classified as having RA. This is the first case to describe high titers anti-PCNA antibodies associated with RA.
Antibodies* ; Arthralgia ; Arthritis, Rheumatoid* ; Autoantibodies ; Autoimmune Diseases ; Blood Sedimentation ; C-Reactive Protein ; Classification ; Female ; Hand ; Humans ; Immunodiffusion ; Joints ; Lupus Erythematosus, Systemic ; Proliferating Cell Nuclear Antigen ; Rheumatic Diseases ; Rheumatoid Factor ; Wrist