Centromere Protein-F-like Pattern in a Patient With Rheumatoid Arthritis

No abstract available.

Preliminary Study on Clinical Utility of Autoimmune Target Test in Psychiatric Disorders

BACKGROUND: Autoantibodies have been detected in patients with psychiatric disorders. However, there is no standard test for the detection of these autoantibodies. In this study, we analyzed autoimmune target (AIT) test results in patients with psychiatric disorders and investigated the clinical utility of the AIT test for psychiatric disorders. METHODS: We retrospectively analyzed data from patients diagnosed with psychiatric disorders between August 1995 and May 2015. Of these, 100 patients assessed using the AIT test were enrolled in this study. Data regarding positive rates, immunofluorescent patterns of AIT results, and the presence of autoimmune diseases in patients with psychiatric disorders were retrospectively collected and analyzed. RESULTS: The autoantibody-positive rate was high in patients with psychiatric disorders (70.0%, 70/100). The positive rates in patients with schizophrenia, depressive disorders, bipolar and related disorders, adjustment disorders, anxiety disorders, and others were 82.9%, 64.7%, 88.9%, 57.1%, 66.7%, and 53.8%, respectively. The most frequent pattern of immunofluorescence was a speckled pattern in 30 cases, followed by microtubule organizing center with microtubule (MTOC-MT) in 17 cases. Twenty-one patients were diagnosed with autoimmune diseases. CONCLUSIONS: In this study, the incidence of autoantibodies was high in patients with psychiatric disorders not specific to schizophrenia. This suggests that the AIT test may therefore have the potential to be a screening test for psychiatric disorders. Further, additional AIT tests in patients with psychiatric disorders may help to clarify the relationships between psychiatric disorders and autoimmune disease.

A Case of Anti-reticulin Antibody-positivity in Metachronous Double Primary Cancer

No abstract available.

The Clinical Utility of the Autoimmune Target Test for Neurologic Disease

BACKGROUND: Many studies have reported the association between several anti-neuronal antibodies and neurologic diseases. However, there is no useful autoantibody screening test for neurologic diseases unlike the antinuclear antibody test for rheumatologic diseases. Hence, we investigated the clinical utility of the autoimmune target (AIT) test as screening test for autoantibodies in neurologic diseases. METHODS: We retrospectively analyzed the results of the AIT test for 375 serum samples of patients diagnosed with several neurologic diseases such as motor neuron disease (MND), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), encephalopathy (EC), polyneuropathy (PN), cerebral ischemic attack, encephalitis, myelitis, epilepsy, and stroke. RESULTS: The overall positive rate of the AIT test in aforementioned diseases was 77.9%. The positive rates for MND, ALS, PD, EC, PN, and the others were 81.3%, 83.9%, 84.8%, 59.3%, 73%, and 75%, respectively. CONCLUSIONS: Our results indicate high positive rates in the AIT test. We believe that the AIT test has potential application for autoantibody screening in the neurologic diseases. We look forward to last as the study about relations between the results of the AIT test and the specific antibodies for neurologic diseases.

Case of Bile Canalicular Antibody in a Korean Patient with Alcoholic Hepatitis

Bile canalicular antibody (BCA) was first reported in 1969. Many studies of BCA were performed in the 1970s and 1980s and revealed that BCA has a highly positive rate in chronic active hepatitis and primary biliary cirrhosis (PBC). These studies suggested that BCA can be useful in the diagnosis of these liver diseases. However, BCA is almost negative in patients with alcoholic hepatitis. We report a case of BCA in a 50-yr-old woman with a history of heavy alcohol consumption. The patient's serum levels of aspartate transaminase and alanine transaminase were increased, leading to a diagnosis of alcoholic hepatitis. The patient was evaluated for liver disease. Anti-mitochondria antibody, anti-smooth muscle antibody, and anti-liver kidney microsomal antibody tests were conducted, yielding negative results. However, during this testing process, the patient's serum was incidentally found to be positive for BCA at a titer of 1:160. This is the first case report of BCA in Korea.

A Case of Smooth Muscle Autoantibody V Pattern in a Patient with Papillary Thyroid Carcinoma

Smooth muscle antibodies (SMAs) are diagnostic markers for the serological diagnosis of type 1 autoimmune hepatitis. SMA that is restricted to staining of the stomach muscle and blood vessel walls was referred to as "SMA-V". In addition, SMAs are classified into the peritubular (SMA-T) and glomerular (SMA-G) patterns. SMAs are occasionally present in patients with malignancies, but have not yet been reported in thyroid cancer. We came across the first case of SMA positivity in a patient with papillary thyroid carcinoma (PTC). A 31-yr-old male was admitted to our hospital for evaluation of incidentally detected thyroid cancer. He had been diagnosed with PTC based on pathological results following fine-needle aspiration biopsy. The patient underwent total thyroidectomy followed by radio-iodine treatment. The serum levels of AST and ALT were increased before radiotherapy. Tests were conducted for the evaluation of liver disease. SMA was positive at a titer of 1:320, showing positive results for the vessel walls but negative results for the glomerulus and tubules in the kidney (SMA-V pattern). The association of SMA with malignancies and the classification of SMA immunofluorescent subtypes have been previously reported. However, these studies have not clearly established the ability of SMA subtype to predict a specific disease. Therefore, evaluation of an association of SMA pattern with specific diseases in SMA-positive patients may provide additional and useful information for the rapid diagnosis and accurate treatment of patients with autoimmune diseases or malignancies. This case report could serve as a great resource for further studies on SMA.

Anti-Proliferating Cell Nuclear Antigen Antibodies Detected in Rheumatoid Arthritis: A Case Report

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.

Atypical Wegener's Granulomatosis Accompanied with Rheumatoid Arthritis: A Case Report

Wegener's granulomatosis (WG) is highly correlated with cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA). Patients with rheumatoid arthritis (RA) rarely contract WG. Although several concurrent cases have been reported overseas, there are no known cases in Korea. Here we report a unique case of RA with atypical WG testing positive for perinuclear ANCA (p-ANCA) and negative for anti-myeloperoxidase (MPO) antibodies. The 62-yr-old female patient presented with multiple joint pain and showed typical blood test results for RA, i.e., an elevated erythrocyte sedimentation rate and C-reactive protein concentration, and positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies. RA was clear based on a total score of 10 when applying the classification criteria developed by the American College of Rheumatology/European League Against Rheumatism (2010). In an autoimmune target test, speckled and skeleton patterns were observed. In an ANCA test, p-ANCA was observed (titer, 1:2,560), and tests for anti-proteinase 3 (PR3) and anti-MPO antibodies were negative. After admission, multiple nodules were detected on a chest X-ray and a computed tomography scan. We suspected that she had rheumatic nodules or vasculitis and performed an open lung biopsy. We detected necrotic granulomatous vasculitis, classified as WG, thus leading to WG diagnosis. In conclusion, WG was diagnosed in an RA patient who was negative for c-ANCA (negative PR3) and positive for p-ANCA (negative anti-MPO), and this peculiar finding is likely to improve diagnosis in cases of RA with atypical WG.

Anti-Rods and Rings Autoantibodies in a Patient With Hepatitis C Virus Infection

No abstract available.

Alterations of Complement C3 and C4 Levels in Delayed Testing

BACKGROUND: In vitro levels of complement C3 and C4 proteins are sensitive to storage conditions. To avoid in vitro complement activation when testing is delayed, serum should be frozen at -20degrees C within 2 hr of venipuncture. However, this is impractical in routine laboratory work. Therefore, we investigated alterations in C3 and C4 levels in refrigerated specimens over time and derived formulae to estimate initial levels of complement concentrations in delayed testing. METHODS: Ten fresh specimens were measured for C3 and C4 concentrations and were refrigerated at 4degrees C. We measured C3 and C4 levels in refrigerated samples daily for 4 days using an automated nephelometer (Beckman Coulter Inc., USA). RESULTS: C3 and C4 levels were significantly increased over time in refrigerated specimens (P<0.001, P<0.001, respectively). The increments in C3 and C4 levels were described by the equations: C3 (mg/dL)=3.55x+87.18 (r=0.9909), and C4 (mg/dL)=0.72x+22.3 (r=0.9395), where x=the number of days samples were refrigerated before testing. Increases in C3 and C4 concentrations were described on a percentage basis by the equations: DeltaC3 (%)=4.14x+1.07 (r=0.9903), and DeltaC4 (%)=3.57x+2.48 (r=0.9405). CONCLUSIONS: As the measured C3 and C4 concentrations increased by 3.55 mg/dL (4.1%) and 0.72 mg/dL (3.6%) per day in refrigerated specimens, the levels of C3 and C4 should be adjusted in delayed testing. We proposed that the formulae presented be used to back-calculate initial levels of C3 and C4 concentrations.

A Case of Thyrotoxicosis with the Presence of Anti-Gastric Parietal Cell Antibodies

The presence of anti-gastric parietal cell antibodies (AGPAs) has been strongly associated with the pathogenesis of pernicious anemia and atrophic gastritis and has been rarely reported in thyrotoxicosis. In addition, AGPAs more commonly occur in the Western population. No case of AGPA occurring in thyrotoxicosis has been reported in Korea to date. We report a case involving the occurrence of AGPAs in a thyrotoxicosis patient examined at the Hanyang University Hospital. Upon medical consultation, a 55-yr-old woman with no significant medical history was found to have elevated levels of cholesterol, AST, ALT, gamma glutamyl transferase, and mild anemia. Further blood tests revealed elevated levels of T3, free T4, and thyroid-stimulating immunoglobulin (TSI), low level of thyroid-stimulating hormone (TSH), and negative results for the anti-thyroid peroxidase antibody (anti-TPO) and anti-thyroglobulin antibody (anti-TG), for which the patient was diagnosed with thyrotoxicosis. To rule out autoimmune hepatitis in the explanation of the continuously elevated levels of AST and ALT, the autoimmune target (AIT), anti-smooth muscle antibody (ASMA), anti-liver/kidney/microsomal antibody (LKM), anti-mitochondria antibody (AMA) and anti-neutrophil cytoplasmic antibody (ANCA) tests were done, and the results were all negative. However, during this process, the patient tested positive for AGPA, when stomach tissue was used as the sample. Finally, the patient was diagnosed with thyrotoxicosis without any other autoimmune disease. This is the first report of confirmed presence of AGPA in a thyrotoxicosis-only patient in Korea.

A Case of Small Cell Lung Carcinoma with Coexisting Autoantibodies against Proliferating Cell Nuclear Antigen and Centriole Detected Using the Autoimmune Target Test

Approximately 60-70% of small cell lung carcinoma (SCLC) cases are diagnosed at extensive stage, thus tumor markers for its early detection are needed. Autoantibodies associated with malignancy are present before radiographic detection. Autoantibodies detected using the autoimmune target (AIT) test in patients with some tumors have shown the possibility of autoantibodies to be used as a tumor marker. To overcome the limitations of antinuclear antibody (ANA) test using HEp-2 cell line, the AIT test was developed using human macrophage cell line, IT-1, as a substrate, which showed positive identification of various autoantibodies with a higher level of sensitivity. We report a case of SCLC with autoantibodies against proliferating cell nuclear antigen (PCNA) and centriole in a 70-yr-old man who had a history of heavy alcohol consumption and a 50 pack-yr history of smoking. Results of computed tomography of the chest and abdomen showed a lung mass and multiple metastases. Extensive stage SCLC was confirmed using sputum cytology and lymph node aspiration biopsy. Anti-PCNA (1:1,280) and anti-centriolar (1:320) patterns were detected using the AIT test. Neuron-specific enolase was elevated (38.2 ng/mL). There was no evidence of systemic autoimmune rheumatic disease or chronic hepatitis. This is the first case report in which coexisting autoantibodies against PCNA and centriole associated with SCLC were detected using the AIT test. This case provides some evidence that autoantibodies may be used as a tumor marker for SCLC.

A Preliminary Study for Applying Antiperinuclear Antibody Test to 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis

BACKGROUND: The American College of Rheumatology/European League against Rheumatism classification criteria for rheumatoid arthritis (ACR/EULAR criteria) include the rheumatoid factor (RF) test and the anti-citrullinated peptide/protein antibody (ACPA) test as serologic makers for rheumatoid arthritis. Antiperinuclear factor (APF) test, an originator of ACPA, is highly specific for rheumatoid arthritis and can be detected in RF or anti-cyclic citrullinated peptide (anti-CCP) negative rheumatoid arthritis, but it is not included in the serologic criterion of ACR/EULAR criteria. In this study, we investigated the way for applying the APF test to ACR/EULAR criteria. METHODS: We analyzed clinical symptoms and laboratory findings of 53 patients who were suspected having rheumatoid arthritis. All patients were negative for the RF and anti-CCP and positive for APF. We classified these patients into 4 groups according to the fluorescence intensity of APF test, and gave 1-4 points for APF positivity. The proportion of patients who scored 6 or greater in ACR/EULAR criteria in relation to APF scores was evaluated. RESULTS: Median scores of ACR/EULAR criteria showed a tendency to increase as the level of fluorescence intensity of APF rises, but ACR/EULAR scores of 4 groups were not different significantly from each other (P>0.05). The proportion of patients who scored 6 or greater in ACR/EULAR criteria were 39.6% and 77.4%, when scores of APF positivity were 2 and 3 points, respectively. CONCLUSIONS: We think it is reasonable to include APF test in the ACPA of ACR/EULAR criteria and give 3 points for APF positivity, regardless of its fluorescence intensity.

The Comparison between Particle Agglutination Assay and Enzyme Immunoassay in the Detection of Mycoplasma pneumoniae-Specific Antibody

BACKGROUND: The two common serological test methods used for initial diagnosis of acute Mycoplasma pneumoniae (MP) pneumonia are particle agglutination assay (PA) and enzyme immunoassay (EIA). We compared the differences between the two methods and suggest a test method more suitable for clinical laboratories. METHODS: A total of 35 patients (18 adult and 17 pediatric) performed MP specific antibody test using PA (Serodia-Myco II, Fujirebio, Japan) and EIA (Ani Labsystems, Finland) methods. IgM and IgG antibodies were measured separately by EIA method. PA and both IgM and IgG EIA were tested in 26 patients and PA and IgG-EIA were tested in 9 patients. RESULTS: The concordance rates between PA and EIA were 57.7% for IgM and 65.7% for IgG antibodies. Positive PA results showed better agreement with IgG (77.8%) than IgM (38.9%), while negative PA results showed better agreement with IgM (100%) than IgG EIA results (25%). In adult patients, the correlation between PA titers and IgM (r=0.852, P <0.01) and IgG values (r=0.517, P <0.05) were statistically significant. In pediatric patients, the correlation between PA titers and IgG values (r=0.842, P <0.01) was statistically significant. CONCLUSIONS: In this study, we observed that PA and EIA may not be used alternatively. Therefore, we suggest that use of both PA and IgM-EIA will be the optimal choice for laboratories. However, when laboratories are required to select one from PA or EIA, PA may be more useful to diagnose MP infection.

Re-evaluation of the Anti-streptolysin O Test for Systemic Rheumatic Diseases

BACKGROUND: Anti-streptolysin O (ASO) test is usually used to diagnose group A streptococcal infection-related diseases, such as rheumatic fever, reactive arthritis, and various infectious diseases. Despite the recent declining incidence of these diseases, ASO test is still frequently performed as a screening test to diagnose rheumatic diseases. This study re-evaluated the clinical usefulness of ASO test in systemic rheumatic diseases (SRD). METHODS: ASO tests was performed in 825 patients between April and October in 2010. ASO levels were compared between SRD and non-SRD groups of patients. The results of ASO, C-reactive protein (CRP), and rheumatoid factor (RF) were compared among 6 subgroups of SRD: rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, Behcet disease, Sjogren's syndrome and others. RESULTS: Positive results in ASO test (>200 IU/mL) were observed in 15.3% (126/825) of the patients tested. None of the ASO positive patients was, however, diagnosed with rheumatic fever or reactive arthritis. There were no statistically significant differences in the mean value (P=0.688) or positive rate (P=0.835) of ASO test between SRD and non-SRD groups. Positive rates of ASO test were also not statistically significant different among six subgroups of SRD patients (all P>0.05), whereas those of CRP and RF tests were significantly different. CONCLUSIONS: The usefulness of ASO test is very low for diagnosing SRD, although it is frequently carried out as a screening test. We suggest that ASO test must be performed selectively when diseases from group A streptococcal infection are suspected.

Comparison of Particle Agglutination Assay and ELISA for Anti-thyroid Autoantibodies

BACKGROUND: Measurements of serum anti-thyroglobulin antibody (anti-Tg) and anti-thyroid peroxidase antibody (anti-TPO) are important for the diagnosis of autoimmune thyroid diseases. Although ELISA is most commonly used for the detection of anti-thyroid autoantibodies, other methods like particle agglutination assay (PA) or radioimmunoassay (RIA) are still being used in clinical laboratories. There are few studies about the comparison between PA and ELISA, and we evaluated the validity of these assays in this study. METHODS: We have used three methods, PA (Fujirebio Inc.), ELISA-1 (Zeus Scientific Inc.), and ELISA-2 (Orgentec Diagnostika) for the measurements of titers or concentrations of anti-thyroid autoantibodies. A total of 212 patients belonging to six different disease groups were tested: 40 patients for anti-Tg only, 64 for anti-TPO (or anti-microsome) only, and 108 for both antibodies. All test results were compared with each other in six disease groups. RESULTS: Concordance of positive or negative results was obtained in 78.5-97.3% of the samples tested, and positive rates of three methods were similar in autoimmume thyroid disease group. In the comparable concentration range, the correlation coefficients were 0.328-0.820 between the two ELISAs or between ELISA and PA. CONCLUSIONS: Positive or negative decisions by three assay systems have high concordance rates, and antibody levels measured by three methods correlate well in the comparable concentration range. The ELISA-1 shows less non-specific reactions, better discrimination in low level of autoantibodies, and the highest positive rate in autoimmume thyroid disease group.

Annual Report on External Quality Assessment in Immunoserology in Korea (2009) / 임상검사와정도관리

The followings are the results for external quality assessment (EQA) in immunoserology for 2009: Evaluation of EQA was done in 2 trials in April and November, about 99% of laboratories participating average 7.4 items. The results were collected via internet and about 98% of laboratories have sent their results via internet. Control materials used in EQA were pooled sera including commercial controls, MASR Immunology Control from Medical Analysis Systems (Camarillo, CA, USA), which were delivered refrigerated for stability of control materials, being received within 48 hours after sending. Latex agglutination tests for rheumatoid factor (RF) showed frequently false positive or false negative results especially in commercial controls, possibly due to matrix effect. False negative and positive results were frequently found in the laboratories using immunochromatography assay (ICA) for anti-HCV and anti-HIV. More careful quality control should be required for ICA tests. New tests measuring non-treponemal and trponemal antibody such as turbidoimmunoassay (TIA) and chemiluminescence immunoassay (CLIA) were introduced. Standardization of instruments and reagents including calibrators for quantitative results should be required for the harmonization of results.

Annual Report on External Quality Assessment in Immunoserology in Korea (2008) / 임상검사와정도관리

The followings are the results for external quality assessment (EQA) in immunoserology for 2008:1.Evaluation of EQA was done in 2 trials in May and November, about 99% of laboratories participating average 7.7 items. The results were collected via internet and about 99% of laboratories have sent their results via internet. 2.Control materials used in the External Proficiecny Testing were pooled sera including Commercial controls, MAS(R) Immunology Control from Medical Analysis Systems (Camarillo, CA, USA), which were delivered refrigerated for stability of control materials, being received within 48 hours after sending. 3.Latex agglutination tests for rheumatoid factor (RF) showed frequently false positive or false negative results especially in Commercial controls, possibly due to matrix effect.4.False negative and positive results were frequently found in the laboratories using immunochromatography assay (ICA) for anti-HCV and anti-HIV. More careful quality control should be required for ICA tests. 5.New tests measuring non-treponemal and trponemal antibody such as turbidoimmunoassay (TIA) and chemiluminescence immunoassay (CLIA) were introduced.6.Standardization of instruments and reagents including calibrators for quantitative results should be required for the harmonization of results.

Annual Report on External Quality Assessment in Immunoserology in Korea (2007) / 임상검사와정도관리

The followings are the results for external quality assessment (EQA) in immunoserology for 2007: 1. Evaluation of EQA was done in 2 trials in May and December, about 99% of laboratories participating average 7.8 items. The results were collected via internet for the first time and 96~98% of laboratories have sent their results via internet. 2. All the specimens for Immunoserology in EQA were delivered refrigerated, being received within 48 hours after sending. 3. Commercial controls, MASR Immunology Control from Medical Analysis Systems (Camarillo, CA, USA) were used to assure the quality of quantitative results of C-reactive protein (CRP), rheumatoid factor (RF) and anti- streptolysin O (ASO) tests, and the RF results of MASR Immunology Control were variable depending on the reagents used. 4. The laboratories using immunochromatography assay (ICA) were increased, however, many laboratories using ICA reported falsely negative for the positive specimens. The sensitivity of ICA test kits as well as various factors influencing the ICA results should be evaluated. 5. The HBsAg results of the ACCURUN 1R Multi-Marker Positive Control (Boston Biomedica Inc. USA) were falsely reported as negative in some laboratories using arbitrarily determined cutoff. 6. Standardization of methods including calibrators for quantitative results should be required for the harmonization of results.

Annual Report on External Quality Assessment in Immunoserology in Korea (2007) / 임상검사와정도관리

The followings are the results for external quality assessment (EQA) in immunoserology for 2007: 1. Evaluation of EQA was done in 2 trials in May and December, about 99% of laboratories participating average 7.8 items. The results were collected via internet for the first time and 96~98% of laboratories have sent their results via internet. 2. All the specimens for Immunoserology in EQA were delivered refrigerated, being received within 48 hours after sending. 3. Commercial controls, MASR Immunology Control from Medical Analysis Systems (Camarillo, CA, USA) were used to assure the quality of quantitative results of C-reactive protein (CRP), rheumatoid factor (RF) and anti- streptolysin O (ASO) tests, and the RF results of MASR Immunology Control were variable depending on the reagents used. 4. The laboratories using immunochromatography assay (ICA) were increased, however, many laboratories using ICA reported falsely negative for the positive specimens. The sensitivity of ICA test kits as well as various factors influencing the ICA results should be evaluated. 5. The HBsAg results of the ACCURUN 1R Multi-Marker Positive Control (Boston Biomedica Inc. USA) were falsely reported as negative in some laboratories using arbitrarily determined cutoff. 6. Standardization of methods including calibrators for quantitative results should be required for the harmonization of results.