1.Presence of serum antinuclear antibodies correlating unfavorable overall survival in patients with chronic lymphocytic leukemia.
Qian SUN ; Li WANG ; Hua-Yuan ZHU ; Yi MIAO ; Wei WU ; Jin-Hua LIANG ; Lei CAO ; Yi XIA ; Jia-Zhu WU ; Yan WANG ; Rong WANG ; Lei FAN ; Wei XU ; Jian-Yong LI
Chinese Medical Journal 2019;132(5):525-533
		                        		
		                        			BACKGROUND:
		                        			Serum antinuclear antibodies (ANAs) are positive in some patients with chronic lymphocytic leukemia (CLL), but the prognostic value of ANAs remains unknown. The aim of this study was to evaluate the role of ANAs as a prognostic factor in CLL.
		                        		
		                        			METHODS:
		                        			This study retrospectively analyzed clinical data from 216 newly diagnosed CLL subjects with ANAs test from 2007 to 2017. Multivariate Cox regression analyses were used to screen the independent prognostic factors related to time to first treatment (TTFT), progression free survival (PFS) and overall survival (OS). Receiver operator characteristic curves and area under the curve (AUC) were utilized to assess the predictive accuracy of ANAs together with other independent factors for OS.
		                        		
		                        			RESULTS:
		                        			The incidence of ANAs abnormality at diagnosis was 13.9%. ANAs positivity and TP53 disruption were independent prognostic indicators for OS. The AUC of positive ANAs together with TP53 disruption was 0.766 (95% confidence interval [CI]: 0.697-0.826), which was significantly larger than that of either TP53 disruption (AUC: 0.706, 95% CI: 0.634-0.772, P = 0.034) or positive ANAs (AUC: 0.595, 95% CI: 0.520-0.668, P < 0.001) in OS prediction. Besides, serum positive ANAs as one additional parameter to CLL-international prognostic index (IPI) obtained superior AUCs in predicting CLL OS than CLL-IPI alone.
		                        		
		                        			CONCLUSION
		                        			This study identified ANAs as an independent prognostic factor for CLL, and further investigations are needed to validate this finding.
		                        		
		                        		
		                        		
		                        			ADP-ribosyl Cyclase 1
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Aged, 80 and over
		                        			;
		                        		
		                        			Antibodies, Antinuclear
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			Autoimmunity
		                        			;
		                        		
		                        			physiology
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Kaplan-Meier Estimate
		                        			;
		                        		
		                        			Leukemia, Lymphocytic, Chronic, B-Cell
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			mortality
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Multivariate Analysis
		                        			;
		                        		
		                        			Mutation
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Proportional Hazards Models
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Survival Analysis
		                        			;
		                        		
		                        			Tumor Suppressor Protein p53
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			Young Adult
		                        			;
		                        		
		                        			ZAP-70 Protein-Tyrosine Kinase
		                        			;
		                        		
		                        			blood
		                        			
		                        		
		                        	
2.Variations of peripheral blood autoantibody, immunoglobuliln, and complement levels in patients with non-lactational mastitis and their clinical significances.
Rui XU ; Qian-Qian GUO ; Le-Ping YANG ; Mi-Lin LAI ; Lin TONG
Journal of Southern Medical University 2016;36(8):1157-1159
OBJECTIVETo detect the variations in peripheral blood levels of autoantibodies, immunoglobulilns and complements in patients with non-lactational mastitis and investigate whether non-lactational mastitis is an autoimmune disease with immune dysfunction.
METHODSSeven-eight patients with non-lactational mastitis treated in our hospital between September 2013 and May 2015 and 88 healthy women (control) were examined for peripheral blood levels of antinuclear antibody (ANA), anti-histone antibody (AHA), immunoglobulins (IgA, IgM, and IgG) and complements (C3, C4, and total complements).
RESULTSs Of the 78 patients with non-lactational mastitis, 50 (64.10%) were positive of ANA showing mainly the granular and cytoplasmic granular fluorescence patterns, and the positivity rate was significantly higher than that in the control group (P<0.000). Twenty-eight (36.00%) of the patients were positive of AHA, a rate significantly higher than that in the control group (P<0.000). The levels of IgA, IgM, C4, and total complements levels were all significantly elevated in the patients compared with those in the control group (P<0.05).
CONCLUSIONPatients with non-lactational mastitis have abnormal changes in peripheral blood levels of immunoglobulins and complements with high positivity rates for ANA and AHA, indicating that non-lactational mastitis is an autoimmune disease with immune dysfunction.
Antibodies, Antinuclear ; blood ; Autoantibodies ; blood ; Autoimmune Diseases ; blood ; diagnosis ; Case-Control Studies ; Complement System Proteins ; analysis ; Female ; Humans ; Mastitis ; blood ; diagnosis
4.A Case of Autoimmune Hepatitis Combined with Graves' Disease.
Jong Hyun JHEE ; Hyun Ju KIM ; Wonseok KANG ; Sewha KIM ; Do Young KIM
The Korean Journal of Gastroenterology 2015;65(1):48-51
		                        		
		                        			
		                        			A 25-year-old woman presented with jaundice, palpitation, and weight loss of 5 kg during a period of 2 weeks. Laboratory tests showed elevated levels of liver enzymes (AST 1,282 IU/L, ALT 1,119 IU/L) and total bilirubin (6.4 mg/dL); negative for hepatitis virus infection; elevated serum levels of triiodothyronine (T3, 3.60 ng/dL), free thyroxine (fT4, 3.82 ng/dL), and lowered serum level of thyroid stimulating hormone (TSH, <0.025 microIU/mL); and positive for thyroid stimulating antibody and anti-mitochondrial antibody (AMA). The liver biopsy findings were consistent with autoimmune hepatitis (AIH). Accordingly, oral steroid therapy was started with 60 mg of prednisolone under the impression of AIH associated with Graves' disease. After a week of steroid therapy, the clinical manifestation showed significant improvement, with normalization of both liver and thyroid functions. Diagnosis of the liver condition of patients who present with hyperthyroidism and liver dysfunction is important, so that appropriate therapy can be promptly initiated.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Alanine Transaminase/analysis
		                        			;
		                        		
		                        			Antibodies, Antinuclear/blood
		                        			;
		                        		
		                        			Aspartate Aminotransferases/analysis
		                        			;
		                        		
		                        			Bilirubin/blood
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Graves Disease/complications/*diagnosis/drug therapy
		                        			;
		                        		
		                        			Hepatitis, Autoimmune/complications/*diagnosis/drug therapy
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Immunoglobulins, Thyroid-Stimulating/blood
		                        			;
		                        		
		                        			Liver/enzymology/metabolism/pathology
		                        			;
		                        		
		                        			Prednisolone/therapeutic use
		                        			;
		                        		
		                        			Steroids/therapeutic use
		                        			;
		                        		
		                        			Thyrotropin/blood
		                        			
		                        		
		                        	
5.A Case of CD4+T-Cell Large Granular Lymphocytic Leukemia.
Jaewook KIM ; Chan Jeoung PARK ; Seongsoo JANG ; Young Uk CHO ; Sang Hyuk PARK ; Eul Ju SEO ; Hyun Sook CHI ; Cheolwon SUH
Annals of Laboratory Medicine 2013;33(3):196-199
		                        		
		                        			
		                        			We report here a case of a 59-yr-old man with CD4+ T-cell large granular lymphocytic leukemia (T-LGL). Peripheral blood examination indicated leukocytosis (45x10(9) cells/L) that consisted of 34% neoplastic lymphoid cells. Other laboratory results indicated no specific abnormalities except for serum antinuclear antibody titer (1:640), glucose (1.39 g/L), and hemoglobin A1c (7.7%) levels. Computed tomography indicated multiple small enlarged lymph nodes (<1 cm in diameter) in both the axillary and inguinal areas, a cutaneous nodule (1.5 cm in diameter) in the left suboccipital area, and mild hepatosplenomegaly. Bone marrow examination revealed hypercellular marrow that consisted of 2.4% neoplastic lymphoid cells. The neoplastic lymphoid cells exhibited a medium size, irregularly shaped nuclei, a moderate amount of cytoplasm, and large granules in the cytoplasm. Immunohistochemical analysis indicated CD3+, CD4+, T-cell receptor betaF1+, granzyme B+, and TIA1+. Flow cytometric analysis of the neoplastic lymphoid cells revealed CD3+, cytoplasmic CD3+, CD4+, and CD7+. Cytogenetic analysis indicated an abnormal karyotype of 46,XY,inv(3)(p21q27),t(12;17)(q24.1;q21),del(13)(q14q22)[2]/46,XY[28]. The patient was diagnosed with CD4+ T-LGL and received chemotherapy (10.0 mg methotrexate). This is the second case of CD4+ T-LGL that has been reported in Korea.
		                        		
		                        		
		                        		
		                        			Antibodies, Antinuclear/analysis
		                        			;
		                        		
		                        			Blood Glucose/analysis
		                        			;
		                        		
		                        			Bone Marrow Cells/metabolism/pathology
		                        			;
		                        		
		                        			Hemoglobin A, Glycosylated/metabolism
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Immunohistochemistry
		                        			;
		                        		
		                        			Immunophenotyping
		                        			;
		                        		
		                        			Karyotyping
		                        			;
		                        		
		                        			Leukemia, Large Granular Lymphocytic/*diagnosis/pathology/radiography
		                        			;
		                        		
		                        			Lymph Nodes/pathology
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Neoplastic Cells, Circulating/metabolism/pathology
		                        			;
		                        		
		                        			Tomography, X-Ray Computed
		                        			
		                        		
		                        	
6.A Case of CD4+T-Cell Large Granular Lymphocytic Leukemia.
Jaewook KIM ; Chan Jeoung PARK ; Seongsoo JANG ; Young Uk CHO ; Sang Hyuk PARK ; Eul Ju SEO ; Hyun Sook CHI ; Cheolwon SUH
Annals of Laboratory Medicine 2013;33(3):196-199
		                        		
		                        			
		                        			We report here a case of a 59-yr-old man with CD4+ T-cell large granular lymphocytic leukemia (T-LGL). Peripheral blood examination indicated leukocytosis (45x10(9) cells/L) that consisted of 34% neoplastic lymphoid cells. Other laboratory results indicated no specific abnormalities except for serum antinuclear antibody titer (1:640), glucose (1.39 g/L), and hemoglobin A1c (7.7%) levels. Computed tomography indicated multiple small enlarged lymph nodes (<1 cm in diameter) in both the axillary and inguinal areas, a cutaneous nodule (1.5 cm in diameter) in the left suboccipital area, and mild hepatosplenomegaly. Bone marrow examination revealed hypercellular marrow that consisted of 2.4% neoplastic lymphoid cells. The neoplastic lymphoid cells exhibited a medium size, irregularly shaped nuclei, a moderate amount of cytoplasm, and large granules in the cytoplasm. Immunohistochemical analysis indicated CD3+, CD4+, T-cell receptor betaF1+, granzyme B+, and TIA1+. Flow cytometric analysis of the neoplastic lymphoid cells revealed CD3+, cytoplasmic CD3+, CD4+, and CD7+. Cytogenetic analysis indicated an abnormal karyotype of 46,XY,inv(3)(p21q27),t(12;17)(q24.1;q21),del(13)(q14q22)[2]/46,XY[28]. The patient was diagnosed with CD4+ T-LGL and received chemotherapy (10.0 mg methotrexate). This is the second case of CD4+ T-LGL that has been reported in Korea.
		                        		
		                        		
		                        		
		                        			Antibodies, Antinuclear/analysis
		                        			;
		                        		
		                        			Blood Glucose/analysis
		                        			;
		                        		
		                        			Bone Marrow Cells/metabolism/pathology
		                        			;
		                        		
		                        			Hemoglobin A, Glycosylated/metabolism
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Immunohistochemistry
		                        			;
		                        		
		                        			Immunophenotyping
		                        			;
		                        		
		                        			Karyotyping
		                        			;
		                        		
		                        			Leukemia, Large Granular Lymphocytic/*diagnosis/pathology/radiography
		                        			;
		                        		
		                        			Lymph Nodes/pathology
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Neoplastic Cells, Circulating/metabolism/pathology
		                        			;
		                        		
		                        			Tomography, X-Ray Computed
		                        			
		                        		
		                        	
7.The clinical features of drug-induced liver injury observed through liver biopsy: focus on relevancy to autoimmune hepatitis.
Hye Young JU ; Jae Young JANG ; Soung Won JEONG ; Sung Ae WOO ; Min Gyu KONG ; Hee Yoon JANG ; Sae Hwan LEE ; Sang Gyune KIM ; Sang Woo CHA ; Young Seok KIM ; Young Deok CHO ; So Young JIN ; Hong Soo KIM ; Boo Sung KIM
Clinical and Molecular Hepatology 2012;18(2):213-218
		                        		
		                        			
		                        			BACKGROUND/AIMS: Accurate diagnosis of drug-induced liver injury (DILI) is difficult without considering the possibility of underlying diseases, especially autoimmune hepatitis (AIH). We investigated the clinical patterns in patients with a history of medication, liver-function abnormalities, and in whom liver biopsy was conducted, focusing on accompaniment by AIH. METHODS: The clinical, serologic, and histologic findings of 29 patients were compared and analyzed. The patients were aged 46.2+/-12.8 years (mean+/-SD), and 72.4% of patient were female. The most common symptom and causal drug were jaundice (58.6%) and herbal medications (55.2%), respectively. RESULTS: Aspartate aminotransferase (AST), alanine aminotransferase, total bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase levels were 662.2+/-574.8 U/L, 905.4+/-794.9 U/L, 12.9+/-10.8 mg/dL, 195.8+/-123.3 U/L, and 255.3+/-280.8 U/L, respectively. According to serologic and histologic findings, 21 cases were diagnosed with DILI and 8 with AIH. The AIH group exhibited significantly higher AST levels (537.1+/-519.1 vs. 1043.3+/-600.5 U/L), globulin levels (2.7+/-0.4 vs. 3.3+/-0.5 g/dL), and prothrombin time (12.9+/-2.4 vs. 15.2+/-3.9 s; P<0.05). Antinuclear antibody was positive in 7 of 21 cases of DILI and all 8 cases of AIH (P=0.002). The simplified AIH score was 3.7+/-0.9 in the DILI group and 6.5+/-0.9 in the AIH group (P<0.001). CONCLUSIONS: Accurate diagnosis is necessary for patients with a history of medication and visits for liver-function abnormalities; in particular, the possibility of AIH should be considered.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Alanine Transaminase/blood
		                        			;
		                        		
		                        			Antibodies, Antinuclear/blood
		                        			;
		                        		
		                        			Aspartate Aminotransferases/blood
		                        			;
		                        		
		                        			Biopsy
		                        			;
		                        		
		                        			Drug-Induced Liver Injury/*diagnosis/pathology
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Globulins/analysis
		                        			;
		                        		
		                        			Hepatitis, Autoimmune/*diagnosis/pathology
		                        			;
		                        		
		                        			Herbal Medicine
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Jaundice/etiology
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Prothrombin Time
		                        			
		                        		
		                        	
8.A Case of Autoimmune Hepatitis Following Acute Hepatitis A.
Young Doo KIM ; Kyung Ah KIM ; Woo Sun ROU ; June Sung LEE ; Tae June SONG ; Won Ki BAE ; Nam Hoon KIM
The Korean Journal of Gastroenterology 2011;57(5):315-318
		                        		
		                        			
		                        			The pathogenesis of autoimmune hepatitis (AIH) is unclear, but viral infections have been proposed as a potential trigger in patients with genetic predisposition. We report a case of AIH following acute hepatitis A (AHA). A 57-year-old woman presented with fatigue and pitting edema for last 3 months. She had been diagnosed as an AHA 15 months ago based on clinical features, biochemical tests and positive HAV IgM antibody at a local clinic. Her biochemical tests was normalized one month after AHA diagnosis, but the serum levels of aminotransferase started to rise four months after AHA diagnosis. Antinuclear antibody was positive at a titer of 1:40, and anti-smooth muscle antibody was also positive. Hypergammaglobulinemia and liver pathology were typical for AIH. The patients had a score of 17 according to the International Autoimmune Hepatitis Group's system. She was given prednisolone and azathioprine and showed complete response to immunosuppressive therapy. The present case is the first report on AIH triggered by AHA in Korea.
		                        		
		                        		
		                        		
		                        			Acute Disease
		                        			;
		                        		
		                        			Alanine Transaminase/blood
		                        			;
		                        		
		                        			Antibodies, Antinuclear/analysis
		                        			;
		                        		
		                        			Aspartate Aminotransferases/blood
		                        			;
		                        		
		                        			Autoantibodies/analysis
		                        			;
		                        		
		                        			Azathioprine/therapeutic use
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Hepatitis A/complications/*drug therapy
		                        			;
		                        		
		                        			Hepatitis, Autoimmune/*diagnosis/drug therapy/etiology
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypergammaglobulinemia/diagnosis
		                        			;
		                        		
		                        			Immunosuppressive Agents/therapeutic use
		                        			;
		                        		
		                        			Liver/pathology
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Prednisolone/therapeutic use
		                        			
		                        		
		                        	
9.Clinical and pathological features of primary biliary cirrhotic patients with negative anti-mitochondria antibody.
Qi-xia WANG ; Lei SHEN ; Xiao-yu CHEN ; De-kai QIU ; Xiong MA
Chinese Journal of Hepatology 2011;19(5):340-344
OBJECTIVETo explore the clinical and pathological features of primary biliary cirrhosis (PBC) patients with negative anti-mitochondria antibody (AMA).
METHODSTwo hundreds and eight PBC patients were enrolled. The clinical and histological data of the negative AMA cases were compared with the AMA/AMA-M2 positive cases.
RESULTS30 out of the 208 cases (14.4%) were AMA negative patients in our study. The general status, biochemical tests and histological findings between the two groups had no significant difference (P > 0.05). The Gamma-globulin, IgG, IgM and IgA levels of AMA/AMA-M2 positive PBC patients were higher than that of the AMA negative cases (P < 0.05). The abnormal rate of cholesterol in AMA negative PBC patients was 65.4% as compared to 50.4% in AMA/AMA-M2 positive cases, no significant difference existed between (P > 0.05). Anti-nuclear antibody (ANA) was observed in 29 (96.7%) AMA negative PBC patients, including 14 (48.3%) with granular pattern, 8 (27.6%) with nuclear membrane pattern, 6 (20.7%) with kinetochore pattern and 1 (3.4%) with homogeneous pattern. AMA negative PBC patients had elevated serum ALP, GGT, IgM and cholesterol levels, and decreased serum AST, IgG and IgA levels as compared with that of autoimmune hepatitis patients (P < 0.05, respectively).
CONCLUSIONIn cholestatic patients with elevated IgM and cholesterol levels, ANA positive with non-homogeneous pattern, the diagnosis of PBC should be suspected, albeit AMA negative. The clinical, biochemical and histological features of the AMA negative PBC patients were similar to classic PBC patients, but quite different from autoimmune hepatitis.
Adult ; Antibodies, Antinuclear ; analysis ; Female ; Humans ; Liver Cirrhosis, Biliary ; immunology ; pathology ; Male ; Middle Aged ; Mitochondria ; immunology ; gamma-Globulins ; metabolism
10.Follow-up and outcome as well as the related biological factors on the cases with indeterminate HIV antibody level.
Yan LI ; Cai-yun LIANG ; Kai GAO ; Zhi-gang HAN ; Bi-lian LUO ; Hui-fang XU
Chinese Journal of Preventive Medicine 2011;45(10):916-919
OBJECTIVETo explore the follow-up visit, outcome and auxiliary diagnosis method on the cases with indeterminate antibody level measured by Western blotting as well as the related biological factors.
METHODSThe cases with indeterminate result were followed up according to the National Guideline for Detection of HIV/AIDS (2009) and samples were collected for HIV antibody detection, p24 antigen and nucleic acid were detected as a supplementary diagnosis at the same time. The samples were also be detected for HBV, HCV, TP, HTLV-I/II, ANA, and AFP, and the results were compared to that of screened positive and confirmed negative cases.
RESULTSA total of 73 were followed up successfully and taken a second HIV test, 25 cases were tested positive and 48 were tested negative for HIV during the follow-up period. For the 25 HIV positive cases, the HIV seroconversion rate was 100.00% at any time point when the interval between the first and returning detection was longer than 1 week. The major Western blotting bands for the cases with indeterminate result were p24 and gp160 and it was different between HIV positive and negative cases in Western blotting band profiles. The consistency and sensitivity of nucleic acid detection were higher than 90.00%, and were higher than that of p24 antigen (69.09% (38/55) and 27.27% (6/22)) (χ(2)(consistency) = 6.875, χ(2)(sensitivity) = 18.893, P < 0.05). The positive rates of ANA and AFP of indeterminate cases excluded from HIV infection were 20.83% (10/28) and 6.25% (3/48) and higher than that of screened positive and confirmed negative cases (0.00%), the difference had statistic significance (χ(2)(ANA) = 19.430, χ(2)(AFP) = 5.520, P < 0.05).
CONCLUSIONIt is critical to get timely diagnosis for the indeterminate cases according to the new national guideline for detection of HIV/AIDS. Nucleic acid detection has higher application value as auxiliary diagnosis for HIV infection than p24 antigen. The increased levels of ANA and AFP may be the factors resulting in the nonspecific indeterminate results.
Antibodies, Antinuclear ; blood ; Female ; Follow-Up Studies ; HIV Antibodies ; blood ; HIV Infections ; diagnosis ; immunology ; Humans ; Male ; alpha-Fetoproteins ; analysis
            
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