Myasthenia gravis (MG) is an autoimmune neuromuscular junction disorders mediated by various autoantibodies. Although most patients with MG require chronic immunosuppressive treatment to control disease activity, appropriate surveillance biomarkers that monitor disease activity or potential toxicity of immunosuppressants are yet to be developed. Herein, we investigated quantitative distribution of peripheral blood B cell subsets and transcriptional profiles of memory B cells (CD19+ CD27+) in several subgroups of MG patients classified according to the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification. This study suggests potential immunologic B-cell markers that may guide treatment decision in future clinical settings.
Americas ; Autoantibodies ; B-Lymphocyte Subsets ; B-Lymphocytes ; Biomarkers ; Classification ; Flow Cytometry ; Humans ; Immunophenotyping ; Immunosuppressive Agents ; Memory ; Myasthenia Gravis ; Neuromuscular Junction Diseases ; Transcriptome

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune muscle diseases with systemic involvement. Patients with IIM present with varying degrees of muscle disease, cutaneous manifestations, and internal organ involvement. The diagnosis and classification of IIM is based primarily on the classification system composed of clinical features, laboratory value and muscle biopsy. In addition, the identification and characterization of myositis-related autoantibodies can help diagnosis and classification. Recently, many studies have also demonstrated that the physician can define the clinical syndromes, establish treatment strategy and predict outcomes based on the patients' myositis-specific autoantibodies (MSA) and myositis-associated antibodies (MAA) profiles. MSAs are found exclusively in IIMs and facilitate the identification of subsets of patients with relatively homogeneous clinical features. MAAs are frequently found in association with other MSA; however, they may also be detected in various connective diseases.
Antibodies ; Antibodies, Antinuclear ; Autoantibodies ; Biopsy ; Classification ; Dermatomyositis ; Diagnosis ; Humans ; Myositis ; Polymyositis

Myasthenia gravis (MG) is a chronic autoimmune disease of neuromuscular blockade, characterized by muscle weakness and fatigue, and is associated with the production of autoantibodies against the skeletal muscle acetylcholine receptor, muscle-specific kinase (MuSK), low-density lipoprotein receptor-related protein 4 (LRP4), and other muscle endplate proteins. In addition, MG may be classified according the location of the affected muscles (ocular vs. generalized), patient age at symptom onset, and thymic pathology. Subgroup classification based on serum antibodies and clinical features include early-onset, late-onset, thymoma-associated, MuSK and LRP4 antibody-negative, and ocular forms of MG, and can help with therapeutic decisions and prognosis. Pyridostigmine is the chosen symptomatic treatment. For patients who do not adequately respond to symptomatic therapy, corticosteroids, other immunomodulating agents, and thymectomy are the first-line immunosuppressive treatments. The treatment of MG is highly individualized and depends on the age of the patient, the type and severity of the disease, and the pace of progression.
Acetylcholine ; Adrenal Cortex Hormones ; Adult ; Antibodies ; Autoantibodies ; Autoimmune Diseases ; Child ; Classification* ; Fatigue ; Humans ; Lipoproteins ; Muscle Weakness ; Muscle, Skeletal ; Muscles ; Myasthenia Gravis* ; Neuromuscular Blockade ; Pathology ; Phosphotransferases ; Prognosis ; Pyridostigmine Bromide ; Thymectomy

Myasthenia gravis (MG) is a chronic autoimmune disease of neuromuscular blockade, characterized by muscle weakness and fatigue, and is associated with the production of autoantibodies against the skeletal muscle acetylcholine receptor, muscle-specific kinase (MuSK), low-density lipoprotein receptor-related protein 4 (LRP4), and other muscle endplate proteins. In addition, MG may be classified according the location of the affected muscles (ocular vs. generalized), patient age at symptom onset, and thymic pathology. Subgroup classification based on serum antibodies and clinical features include early-onset, late-onset, thymoma-associated, MuSK and LRP4 antibody-negative, and ocular forms of MG, and can help with therapeutic decisions and prognosis. Pyridostigmine is the chosen symptomatic treatment. For patients who do not adequately respond to symptomatic therapy, corticosteroids, other immunomodulating agents, and thymectomy are the first-line immunosuppressive treatments. The treatment of MG is highly individualized and depends on the age of the patient, the type and severity of the disease, and the pace of progression.
Acetylcholine ; Adrenal Cortex Hormones ; Adult ; Antibodies ; Autoantibodies ; Autoimmune Diseases ; Child ; Classification* ; Fatigue ; Humans ; Lipoproteins ; Muscle Weakness ; Muscle, Skeletal ; Muscles ; Myasthenia Gravis* ; Neuromuscular Blockade ; Pathology ; Phosphotransferases ; Prognosis ; Pyridostigmine Bromide ; Thymectomy

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

Systemic sclerosis (SSc) is a connective tissue disease of unknown origin, which is characterized by fibrosis of the skin and internal organs, and endothelial and immunologic dysfunction. The presence of a wide range of symptoms renders disease classification difficult. Although recent studies have contributed to our understanding of this debilitating illness, well-validated classification criteria are required for accurate comparison between registries and clinical trials, to assess response to treatment, morbidity and prognosis. Given the emphasis placed upon early and aggressive treatment, the 1980 American College of Rheumatology (ACR) classification criteria are of limited utility with respect to early diagnosis of SSc and limited cutaneous SSc. Recently, the 2013 ACR/European League Against Rheumatism classification criteria for SSc were published for research and clinical practice purposes. These criteria include skin thickening, fingertip lesions, telangiectasia, abnormal nailfold capillaries, Raynaud's phenomenon, SSc-specific autoantibodies and pulmonary complications pertaining to vasculopathy, autoimmunity and fibrosis. These updated criteria should allow a greater number of patients to receive an early diagnosis of SSc.
Autoantibodies ; Autoimmunity ; Capillaries ; Classification* ; Connective Tissue Diseases ; Diagnosis ; Early Diagnosis* ; Fibrosis ; Humans ; Prognosis ; Registries ; Rheumatic Diseases ; Rheumatology ; Scleroderma, Systemic* ; Skin ; Telangiectasis

Systemic lupus erythematosus (SLE) is a prototype for multi-system, autoimmune diseases of unknown etiology, characterized by the production of autoantibodies. SLE can involve any organ system of the body with constitutional symptoms, including musculoskeletal, skin, renal, neuropsychiatric, cardiovascular, respiratory and gastrointestinal systems. These wide spectra of disease manifestations have made disease classification difficult. American College of Rheumatology (ACR) proposed classification criteria for SLE for research purpose in 1982, which had been widely used for research purpose and not for diagnosis. In 1997, these criteria were updated with further recognition of antiphospholipid antibodies, but not validated. But ACR criteria didn't still meet the necessity for earlier diagnosis of SLE. In order to improve clinical relevance and incorporate new knowledge to the field of lupus immunology, the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC), an international lupus expert group dedicated to clinical research on lupus, revised the ACR systemic lupus classification criteria in 2012. The new 2012 SLICC criteria were validated using a large set of patient scenarios rated by experts. The history and diagnostic utility of SLE criteria are covered in this review.
Allergy and Immunology ; Antibodies, Antiphospholipid ; Autoantibodies ; Autoimmune Diseases ; Classification* ; Diagnosis ; Humans ; Lupus Erythematosus, Systemic* ; Rheumatology ; Skin

PURPOSE: With rising obesity rates in children, it is increasingly difficult to differentiate between type 1 and type 2 diabetes mellitus (T1DM, T2DM) on clinical grounds alone. Using C-peptide as a method of classifying diabetes mellitus (DM) has been suggested. This study aimed to find a correlation between fasting C-peptide level and DM types in children and adolescents. METHODS: A total of 223 diabetic children, newly diagnosed at 5 hospitals between January 2001 and December 2012, were enrolled in this study. Initial DM classification was based on clinical and laboratory data including fasting C-peptide at diagnosis; final classification was based on additional data (pancreatic autoantibodies, human leukocyte antigen type, and clinical course). RESULTS: Of 223 diabetic children, 140 were diagnosed with T1DM (62.8%) and the remaining 83 with T2DM (37.2%). The mean serum C-peptide level was significantly lower in children with T1DM (0.80 ng/mL) than in children with T2DM (3.91 ng/mL). Among 223 children, 54 had a serum C-peptide level <0.6 ng/mL; they were all diagnosed with T1DM. The proportion of children with T2DM increased in accordance with C-peptide level. Forty-nine of 223 children had a C-peptide level >3.0 ng/mL; 48 of them (97.9%) were diagnosed with T2DM. CONCLUSION: In this study, we found that if the C-peptide level was <0.6 ng/mL at diagnosis, T2DM could be excluded; if C-peptide level was >3.0 ng/mL, a T1DM diagnosis is unlikely. This finding suggests that serum fasting C-peptide level is useful for classifying DM type at the time of diagnosis in youth.
Adolescent* ; Autoantibodies ; C-Peptide* ; Child* ; Classification* ; Diabetes Mellitus* ; Diabetes Mellitus, Type 2 ; Diagnosis ; Fasting* ; Humans ; Leukocytes ; Obesity

Diabetes among young patients in Korea is caused by a complex set of factors. In addition to the typical T1aD and T2D patients, there is a variable incidence of cases of non-autoimmune types of T1D associated with insulin deficiency (T1b), such as fulminant T1D (FT1D). Although T1a is the major type of childhood diabetes, FT1D exists as a hyper-acute subtype of T1D that affects older children, without causing autoimmunity. They showed a complete loss of beta-cell secretory capacity without evidence of recovery, necessitating long-term treatment with insulin. In addition, latent autoimmune diabetes in adults (LADA) is a form of autoimmune-mediated diabetes, usually diagnosed based on GAD autoantibody positivity. Although many epidemiological surveys of LADA have been conducted in Caucasian and Asian populations, their reported prevalence rates vary due to the use of different diagnostic criteria. In a recent study with a comparable design and valid methodology, the prevalence of LADA using GAD autoantibody positivity as the diagnostic criterion was higher (4.4%) than the previously reported prevalence of 1.7% in a population-based T2D survey. After 36 months of follow-up, only 3 of the 39 patients initially diagnosed with LADA had become insulin-dependent, and they were all positive for multiple autoantibodies (GAD, IA-2 and ZnT8 antibody). This demonstrates that true insulin dependency, which was initially indicated by multiple antibody positivity, has not increased in the Korean population. Therefore, despite etiological heterogeneity, in the clinical setting, early diagnosis and classification of patients with diabetes relying on clinical grounds without measuring autoantibodies could be a possible method to minimize complications.
Adult ; Asian Continental Ancestry Group ; Autoantibodies ; Autoimmunity ; Child ; Classification ; Diabetes Mellitus, Type 1 ; Early Diagnosis ; Follow-Up Studies ; Genetic Heterogeneity ; Humans ; Incidence ; Insulin ; Korea ; Population Characteristics* ; Prevalence

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