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Objective To investigate the change of CD35 expression on neutrophils in the peripheral blood and the relationship between the change and disease activity in patient with myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis (MPO-AAV).Methods Forty untreated patients with active MPO-AAV(patient group)and forty healthy volunteers (control group) were enrolled into this study,and Bermingham vasculitis activity score (BVAS) for every patient was recorded.Flow cytometry (FCM) was employed to detect the CD35 and MPO expression on the neurtrophil,and enzyme linked immunosorbent assay (ELISA) was taken to test the levels of autoantibody against MPO-Antineutrophil cytoplasmic antibody (MPO-ANCA),fragment a from the activated complement factor B (Ba) and MPO in peripheral blood from both group.All test results were compared between the 2 groups by t test,Non-parametric test,Spearman correlation analysis.In addition,the relations among the laboratory results and the relationship between BVAS and the laboratory results were analyzed respectively.Results Compared with the control group,the expression level,which was represented as mean flourscence indensity (MFI),of CD35 and neutrophil membrane MPO on peripheral blood neutrophils was significantly increased [(2 014±968) vs (1 454±511),t=3.024,P=0.002 and (709±244) vs (580±158),t=2.806,P＜0.01,respectively],and the MPO expression level in neutrophils was significantly lower [(1 525±1 033) vs (3 196±2 126),t=-4.468,P＜0.01].Ba and MPO levels in serum of the patient group was significantly higher than that in the control group [37.89(26.17,63.14) μg/L vs 27.99(18.64,46.52) μg/L,Z=-2.521,P=0.012 and 546.16(450.55,729.96) U/L vs 327.93(279.02,365.10) U/L,Z=7.121,P＜0.01,respectively].In patient group,the expression level of CD35 had a significant positive relationship with peripheral blood neutrophil count (r=0.573,P＜0.01),serum Ba (r=0.433,P=0.005) and BVAS (r=0.368,P=0.020),respectively,whereas,there was a negative correlation between the MPO expressed on the neutrophils and that in the neutrophils (r=-0.458,P=0.003),and a positive relationship between MPO-ANCA and BVAS (r=0.351,P=0.026).Conclusion There is significant increased expression of CD35 on the neutrophil of patient with MPO-AAV,which might protect the neutrophil from destruction by the activated complement alternative pathway,and more neutrophils consequently contribute to the MPO-AAV pathogenesis.Inhibition of CD35 expression might become one of the potential new pathways for the treatment of MPO-AAV.
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Objective To investigate the expression of CD55 and myeloperoxidase (MPO) on neutrophils in patients with MPO-specific anti-neutrophil cytoplasmic antibody associated vasculitis(MPO-AAV), and analyze the relationship between the expression and clinical manifestation.Methods Forty untreated patients with active MPO-AAV (patient group) and 30 healthy volunteers (control group) were enrolled in this study.The CD55 on neutrophils and both membrane and cytoplasmic MPO were detected by flow cytometry.Serum fragment-from the activated complement factor B(Ba) and MPO were measured by ELISA.The clinical activity of vasculitis was valued by Birmingham vasculitis activity score-version 3(BVAS-V3).The significance of laboratory data was evaluated by Spearman correlation test and multivariate linear regression analysis.Results (1)The mean fluorescence intensity(MFI) of CD55 expressed on neutrophils was significantly higher than that in control group[4 068.6±2 306.0 vs 2 999.5±1 504.9,P=0.033].Similar results of serum MPO and Ba in patient group were found compared to controls [500.0(381.0, 612.7) IU/L vs 286.9(225.5, 329.1) IU/L,P<0.001;35.2(25.2, 79.5) ng/L vs 18.0(15.0, 28.0) ng/L,P<0.001], respectively.However, MIF of cytoplasmic MPO in patients was significantly lower than that of control group(1 577.1±1 175.9 vs 3 105.3±2 323.0,P=0.003).(2) In patient group, cytoplasmic intensity of MPO was negatively associated with the serum levels of MPO(r=-0.710,P<0.001) and Ba (r=-0.589,P=0.001).Moreover, serum MPO was positively associated with serum Ba(r=0.691,P<0.001).Membrane intensity of CD55 on neutrophils was positively correlated with patient age (r=0.514, P=0.001), C reactive protein (r=0.376, P=0.018), peripheral neutrophils count (r=0.485, P=0.001) and BVAS-V3 (r=0.484, P=0.002), whereas negative correlation between membrane CD55 and disease duration was seen (r=-0.403,P=0.01).(3) The result of multiple linear regression analysis showed there was statistically significant positive correlation between MFI of CD55 expressed on neutrophils and BVAS-V3 (β=0.001,P=0.027).Conclusions In MPO-AAV,CD55 expression on neutrophils is markedly enhanced, which is one of the independent risk factors related to disease activity.It might protect neutrophils from attacking AAV, CD55 expression on neutrophils is markedly enhanced, which is one of the independent risk factors related to disease activity.It might protect neutrophils from attacking by complement alternative pathway.Activated neutrophils release more MPO and lysosome to intensify the inflammation reaction and aggravate the disease.Thus CD55 might become a new potential target for the treatment of this disease in the future.
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Objective To determine the levels and significance of Krebs von den lungen-6(KL-6), pulmonary surfactant protein A (SP-A), SP-D and interleukin (IL)-6 in patients with connective tissue disease interstitial lung disease (CTD-ILD). Methods The serum KL-6, SP-A, SP-D and IL-6 in all subjects were detected and the imaging and pulmonary function were recorded t test, χ2 test, non-parametric test, ANOVA and correlation analysis were used for data analysis. Results ① The levels of serum KL-6, SP-A, SP-D, IL-6 in the CTD-ILD group [551.4 (428.2, 883.5) U/ml, 938.4(435.2, 2324.7) pg/ml, 90.7 (80.7, 100.3) ng/ml and 30.4 (22.9, 41.7) pg/ml; P all<0.05] was significantly higher than that in the CTD group [192.9 (139.2, 266.2) U/ml; 458.0 (372.6, 529.0) pg/ml; 80.0 (71.2, 98.3) ng/ml; 18.6 (4.9, 31.0) pg/ml, Z=-5.383, -3.76, -2.123,-3.903, P all <0.05]; and higher than healthy controls (n=30) [183.2(141.9, 216.6) U/ml; 229.0(162.0, 248.0) pg/ml;50.8(26.1, 96.4) ng/ml;7.1(3.7, 8.7) pg/ml, Z=-5.801,-8.13, 2.272, 3.266;P all<0.05].②The levels of KL-6 in pulmonary HRCT for active ILD group was significantly higher than the non-active ILD group [998.5 (640.3, 1293.3) U/ml vs 565.0(434.0, 799.5) U/ml, Z=2.182, P=0.023], there was no statistical difference in the levels of SP-A, SP-D, IL-6 between the 2 groups. ③ Spearman correlation analysis showed that KL-6 was negatively correlated with forced vital capacity (FVC%);SP-D, IL-6 and diffusing capacity of carbon monoxide (DLCO %). ④ Logistic multiple regression analysis showed that KL-6 [OR=1.017, P=0.002, 95%CI (1.006, 1.028)], SP-A [OR=1.023, P=0.009, 95%CI (1.006, 1.041)], SP-D [OR=1.175, P=0.009, 95%CI (1.075, 1.264)], IL-6[OR=1.213, P=0.001, 95%CI(1.088, 1.354)] were the risk factors for ILD. Conclusion Serum KL-6, SP-A, SP-D and IL-6 are significantly increased and correlate with CTD-ILD. KL-6 is related to the pulmonary inflammatory disease and vital capacity, while SP-D and IL-6 are related to diffusion function.
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Objective To explore preliminarily the role of the E2 subunit of pymvate dehydrogenase (PDC-E2) modified by xenobiotics (e.g.2-octynic acid,2-OA) in the pathogenesis of primary biliary cirrhosis (PBC).Methods Patients of PBC (102 cases),primary sclerosing cholangitis (PSC,34 cases) and healthy controls (HC,50 cases) were selected.The anti-PDC-E2,anti-2-OA and anti-lipoic acid (LA) antibody in the peripheral blood of the 3 groups were tested by enzyme linked immunosorbent assay (ELISA).By inhibitive ELISA (iELISA),30 of the 102 PBC patients with anti-PDC-E2 antibody but without anti-2-OA antibody were selected to detect whether there was any new epitope on the PEC-E2 conjugated with 2-OA.The chi-square test and Fisher exact test were taken to analyze the enumeration data.The two-tailed unpaired t test with Welch's correction was used to compare the measurement data.Spearman rank correlation analysis was also employed for proper test.Results The positive rate of anti-PDC-E2,anti-LA and anti-2-OA antibody in PBC patients was 94.1％(96/102),73.5％(73/102) and 53.9％(55/102) respectively,all of which were statistically significantly higher than those in healthy controls group but were of no significant difference between PSC and healthy controls group.There was no significant relevance between the levels of Anti-LA and anti-2-OA antibody in the PBC group (r=-0.065,P=0.520).The iELISA results showed that the antibody,which only identified the epitopes on 2-OA-PDC-E2 induced by the 2-OA conjugation with PDC-E2,existed in 40％(12/30) of the PBC patients,and more interestingly,this antibody was predominantly appeared in PBC patients at their early clinical stage.Conclusion There are anti-LA antibody and anti-2-OA antibody in PBC patients,which have shown no significant association with each other.It is very likely that new antigenic conformational epitopes on PDC-E2 modified by 2-OA would emerge,which might led to the immune response in the individuals who are susceptible to PBC,and thus contribute for the breaking of PDC-E2 immune tolerance,and PBC occurrence finally.
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Objective To investigate the relationship between complement C3 level and the degree of disease activity in patients with systemic lupus erythematosus(SLE).Methods A total of 1 012 patients with SLE were enrolled in this study from January 2006 to December 2013 at department of rheumatology and immunology,the first affiliated hospital of Anhui medical university.Serum complement C3 level was detected by rate erythenephelometry assay.The relationship between reduction of complement C3 and SLE was analyzed.Results Serum complement C3 clearly decreased in 782 patients,accounted for 77.27％.There were significant differences concerning serum complement C3 level among different groups of disease activity (F =131.275,P＜0.01).The low serum complement C3 level was correlated with the high degree of disease activity (r =-0.517,P ＜0.01).Patients with SLE had a severe disease activity (SLE disease activity index ≥ 15) when the level of serum complement C3 was less than 0.57 g/L.Serum complement C3 levels were positively correlated with serum complement C4 (r =0.845,P ＜ 0.01),peripheral blood leukocyte count (r =0.115,P ＜ 0.01),hemoglobin (r =0.069,P ＜ 0.01),platelet count (r =0.177,P ＜0.01) and albumin level (r =0.091,P ＜ 0.01).There was also a negative association of serum complement C3 with 24 h urinary protein (r =-0.228,P ＜ 0.01).101 patients whose average level of serum complement C3 was(0.48 ±0.26)g/L,were treated with glucocorticoid pulse therapy as high degree of disease activity.Conclusions There is a close relationship between serum complement C3 level and the degree of disease activity in SLE.Serum complement C3 less than 0.57 g/L might be seen in SLE with severe disease activity.
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Objective To investigate the clinical characteristics of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (MPO-AAV) with pulmonary injury and the relationship between pulmonary injury and ANCA against light chain of MPO (LCMPO-ANCA).Methods A total of 195 patients with newly diagnosed primary active MPO-AAV were recruited in this prospective study.Indirect immunofiuorescence assay was used to detect peri-nuclear ANCA (p-ANCA).Immunoblotting and ELISA were used to detect myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA).Clinical features of patients with both positive p-ANCA and MPO-ANCA were collected.Disease activity was evaluated by Birmingham Vasculitis Activity Score-version 3 (BVAS-V3) Recombinant light chain of MPO was used to coat substrate of LCMPO-ANCA by ELISA.The clinical characteristics of pulmonary injury and its correlation with serum levels of p-ANCA,MPO-ANCA and LCMPO-ANCA were explored.Results All 195 patients (64 male and 131 female),consisted of 191 patients (98.0％) with microscopic polyangiitis,3 patients (1.5％) with granulomatosis with polyangiitis,and 1 (0.5％) with eosinophilic granulomatosis with polyangiitis including 64 men and 131 women.Their mean age was (63.2 ±13.5) years old.The level of MPO-ANCA had a positive correlation with general BVAS-V3 (r =0.193,P =0.007) in all patients,and the level of LCMPO-ANCA was positively related with the pulmonary BVAS-V3 (r =0.228,P =0.001).As for multiple systemic damages,the incidence of lung involvement was 60.51％(118/195),which ranked second to renal involvement (71.80％,140/195).The most common pulmonary injuries represented as pulmonary infiltration of 80.51％ (95/118),pleural effusion / pleurisy of 41.53％(49/118),pulmonary nodule or cavity of 22.03％ (26/118).Compared with those without lung involvement,the patients with pulmonary injuries were older [(66.39 ± 10.70) years old vs (58.30 ±15.72) years old;t =4.277,P =0.001],had a shorter course of disease [2.00(1.00,10.50) months vs 3.00(1.00,3.50) months;t =-2.283,P=0.024],and higher scores of general BVAS-V3 (18.21 ±6.08 vs 15.18 ± 5.64;t =3.501,P =0.001).Also,in the patients with pulmonary lesions,the positive rate of LCMPO-ANCA was significantly higher (35.59％ vs 6.49％;x2 =21.569,P ＜ 0.001),and the level of LCMPO-ANCA was significantly higher (0.377 ±0.229 vs 0.285 ±0.079;t =3.399,P =0.001)than those without lung involvement.The pulmonary BVAS-V3 in the patients with LCMPO-ANCA was significantly higher than that in the patients without LCMPO-ANCA (4.34 ± 2.10 vs 2.59 ± 2.52;t =4.301,P ＜ 0.001),whereas the pulmonary BVAS-V3 was not correlated with LCMPO-ANCA (r =0.035,P =0.708) in patients with lung injuries.Conclusion Pulmonary injury was relatively common and insidious in patients with MPO-AAV.To monitor ANCA level is necessary in patients with pulmonary injury.LCMPO-ANCA might play an important role in the pathogenesis of pulmonary lesions in AAV.
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Objective To test the level of cell factor interleukin (IL)-21,CXCL13 in the plasma of patients with rheumatoid arthritis (RA),and to analyze the relationship between Follicular helper T cells(Tfh)and clinic features and discuss the possible immunological pathogenesis of RA.Methods The Tfh cells were obtained from patients and healthy controls (NC) and detected by Flow cytometery.While the levels of IL-21,CXCL13 in patients and NC were measured by ELISA tests.Those analysis were performed by student's t-test,one-way ANOVA,SNK-q test,Chi-square test,Spearman's correlation and multiple linear regression.Results The expression of CD4+CXCR5+ICOS+ cells (Tfh) in PBMCs of RA was significantly higher than normal controls (3.0±1.2 vs 1.1±0.4,P＜0.01).Meanwhile,the three RA groups of patients were divided to low,moderate and high disease activity groups,and the results showed that the expression of Tfh were increased accordingly (1.8±0.7,2.5±0.6,4.0±1.2).The expression of Tfh in the three groups were all significantly higher than that of controls (P＜0.01).There was a positive correlation between Tfh and DAS28,ESR,CRP,TJC,and bone erosion,RF and anti-CCP respectively.The expression of Tfh in those patients who had bone destruction was higher than those with no or mild bone destructions (2.7±1.1vs 3.4±1.3).The expression of Tfh in patients with un-treated RA patients,when compared to those RA patients who were treated appropriately and those who were not treated appropriately,was decreased significantly.The expression of Tfh in appropriately treated RA patients was lower than that without appropriately treatment.The level of IL-21,CXCL13 was decreased in patients with RA in the order of high,moderate,low disease activity and NC.Conclusion The expression of Tfh and the levels of IL-21,CXCL13 are increased significantly,and are closely related to disease activity and bone ersions.The expression of Tfh is decreased after relevant treatment.These results indicate that the abnormality of Tfh may play an important role in the pathogenesis of RA.
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ObjectiveTo investigate the clinical characteristics and predisposing factors of systemic lupus erythematosus(SLE) with sepsis.MethodsTwenty-one SLE patients with sepsis admitted to our hospital between 2005-2010 were reviewed in this study.The other 21 inpatients with active SLE in our hospital in the same period were randomly selected as controls.Clinical and laboratory documents of these patients were comparatively analyzed.Results The peak body temperature [ (39.4±0.6) vs (37.2±0.4) ℃,t=13.403,P=0.000],the hyperpyrexia (T≥39 ℃) incidence (71％ vs 5％,X2=19.788,P=0.000),the white blood cell (WBC) counts[(10.2±4.6) vs(6.2±2.5)×109/L,t=3.469,P=0.001)] and neutrophils in the peripheral blood [(8.3±4.5) vs(4.5±2.1)×109/L,t=3.559,P=0.001 ],the C-reactive protein(CRP) level [ (74±59) vs (5±4) mg/L,t=5.398,P=0.000 ] and lactate dehydrogenase (LDH) level[ (444±343) vs ( 225±144) U/L,t=5.398,P=0.000] in the sepsis group were significantly higher than those in the control group.It was noticeable that CRP in the sepsis group was 15 to 20 times higher than that in the control group.The level of serum albumin[ (29±9) vs(35±7) g/L,t=2.688,P=0.011 ],the maintenance dosage of hydroxychloroquine [(0.11±0.08) vs(0.17±0.09) g/d,t=2.331,P=0.025],the frequency of autoantibodies against SSA (38％ vs 71％,X2=4.709,P=0.03) or SSB(0 vs 43％,X2=11.455,P=0.001) in the sepsis group were significantly lower than those in the control group.Correlation analysis showed that,in the sepsis group,the SLE disease activity index (SLEDAI) had significant positive association with SLE duration (r=0.514,P=0.017),the WBC count (r=0.552,P=0.010) and neutrophils count(r=0.545,P=0.011 ),respectively.The neutrophil count correlated positively with the LDH(r=0.482,P=0.032) and CRP(r=0.606,P=0.022).These correlations were not statistically significant in the control group.ConclusionSepsis should be considered when SLE patients have hyperpyrexia,high levels of WBC and neutrophils,markedly elevated LDH and CRP level,especially when the CRP increases ten times higher than the normal limit.SLE activity and sepsis might affect each other,and this may be more evident in patients with longer disease duration.Hypoalbuminemia and negative autoantibody to SSA or SSB are likely to be the risk factors for SLE to develop sepsis while hydroxcyhloroquine may be protective against sepsis.
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Objective To characterize the clinical characteristics of lupus mesenteric vasculitis (LMV). Methods Analyzing the clinical, laboratory and treatment data of LMV patients hospitalized from 2002. 1.1 to 2007. 12. 31 retrospectively. Results (1) The three common manifestations were abdominal pain, diarrhea and vomit with the prevalence rate of 77%, 70% and 67% respectively. (2)The majority of LMV cases were active vital organ (28/30), kidney (24/30) and hematological system (18/30) were the main organs of involvement. Ten patients had hydroureteronephrosis, and 8 patients had intestinal pseudo-obstruction at the same time. (3) Systemic lupus erythematosus disease activity index (SLEDAI) score was ≥10 in 80% (24/30) of patients. The progression of LMV was accompanied with new-onset ieucopenia or worsening leucopenia or hypocomplementemia in 10 cases. (4) Blood antinuclear antibodies were positive in 27 patients detected, and anti-SSA antibody was positive in 15 (56%), anti-U1RNP antibody was positive in 14 (52%). (5) Fourteen cases had bowel wall thickening with target sign or mesenteric vessels with palisade or comb sign in contrast CT scan of abdomen. (6)Twenty-seven cases were treated with orally or intravenous medium to high dose steroid therapy and recovered from LMV. Conclusions (1) Abdominal pain, diarrhea and vomit were frequent manifestations of LMV patients. (2) LMV was one of the serious complications of systemic lupus erythematosus(SLE), and usually accompanied by active SLE in other organs. (3) A drop in the white blood cell count or complement C3 titer might be correlate with the occurrence of LMV. It needs to further investigate the relationship between LMV and the high positive rate of anti-SSA and anti-U1RNP antibody. (4) LMV patients responded well to intravenous high dose methylprednisolone.
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<p><b>OBJECTIVE</b>To explore the possible genetic model of psoriasis vulgaris.</p><p><b>METHODS</b>The complex segregation analysis and heritability calculation were performed with the aid of Penrose method, Falconer regression method and SAGE-REGTL program.</p><p><b>RESULTS</b>It was found that in 1043 patients with psoriasis vulgaris, 305 patients (29.24%) have the family history of psoriasis, and 738 patients have not the family history. A ratio of s/q approached 1/(square root of q) with Penrose method, and the heritability values of psoriasis in the first-degree and second-degree relatives were 67.04%, 46.6% respectively. By complex segregation analysis, Mendelian, non-major-gene model and environment model were rejected for psoriasis.</p><p><b>CONCLUSION</b>The results suggest that psoriasis follows a pattern of polygenetic or multifactorial inheritance rather than single-gene inheritance.</p>
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Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Data Interpretation, Statistical , Family Health , Models, Genetic , Psoriasis , GeneticsABSTRACT
Objective To investigate the effects of genetic factors on the onset of psoriasis. Methods Seven hundred and twenty patients with psoriasis vulgaris were studied by questionnaire. Results① For the male and female patients, the peak ages of the first onset were 20～ 29 and 10～ 19 years, respectively, and the average ages were 27.57? 12.18 and 23.01? 12.40 years, respectively.② In 720 psoriatics, 212 cases (29.4％ ) reported to have a family history of psoriasis. The age of onset was earlier in man with family history than that in man without family history (P0.05).④ The heritabilities of psoriasis were 71.07％? 2.05％ in first degree relatives and 36.77％? 5.17％ in second degree relatives. Conclusion The results show that psoriasis vulgaris may be a multigenic inheritable disease, and the genetic factors play an important role in the pathogenesis.
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Objective To investigate the role of skin homing T lymphocytes in the development of psoriasis vulgaris(PV). Methods Indirect immunofluorescent double staining technique was employed to study the expression of infiltrating skin homing T lymphocytes in normal, uninvolved perilesional and lesional psoriatic skin in different stages (progressing, stable or regressing) and in normal human skin. Results ①Expression of cutaneous lymphocyte associated antigen (CLA) was found in the majority of CD3+T lymphocytes in normal human skin and in lesions of PV, and CD45RO phenotype was expressed in almost all CLA+T lymphocytes. ②In psoriatic lesions, the number of CD4+CLA+and CD8+CLA+cells was higher in progressive stage than that in stable stage(P