Objective To assess the effectiveness and safety of oral administration of type Ⅱ collagen(C Ⅱ) versus placebo in patients with active rheumatoid arthritis(RA).Methods Seventy patients with active RA were randomly divided into receive placebo(n=35) or bovine CⅡ(n=35) at 0 1mg/day for 12 weeks,in a double-blind study.The cumulative response rates were analyzed by utilizing the American College of Rheumatology(ACR) criteria for improvement in RA,and the requirement for ≥50% improvement of outcome measures in ACR criteria.Results After the 12-week course of treatment,much more outcome was significantly improved in C Ⅱ group than in placebo group.The rates of improvement and remarkable improvement in CⅡ group were increased significantly,as compared with placebo group(54 55% vs 12 12% and 18 18% vs 3 13%,respectively,P0 05).Conclusions Oral administration of CⅡ in treating RA was significantly effective and has slight side effects.Further investigation in the field is worthwhile.

Objective Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis(AAV)is a systemic necrotizing small-vessel vasculitis, and myeloperoxidase(MPO) is one of the main antigens that ANCA can recognize.This study was to investigate the clinical significance of MPO, activated complement C5a fragment and ceruloplasmin ( Cp) in the peripheral blood of patients with MPO-ANCA associated vasculitis ( MPO-AAV) in active phase by observing their changes. Methods 132 MPO-AAV patients at active stage were selected as the patient group, while the control group was made up of 30 healthy controls.Peri-nuclear ANCA (p-ANCA) and MPO-ANCA in the patient group were detected by IIF and ELISA, respectively.The levels of MPO, Cp and C5a in both groups were tested by ELISA.The Birmingham vasculitis activity score (BVAS) of every patient was calculated.In the patient group, the relationship among MPO, Cp, C5a and MPO-ANCA were analysed, and the association between BVAS and each of them was also explored. Results The levels of MPO, CP, C5a in the patient group were significantly higher than those in the health control group [MPO:400.7(333.5~506.1) vs 286.9(225.5~329.1)IU/L, P<0.001;C5a:336.7 (277.6~403.5) vs 236.8 (204.2~304.1) ng/mL, P<0.001;Cp:481.1 (387.9~535.9) vs 326.9 (177.1~405.5) ng/mL,P<0.001].The associations between MPO and Cp, C5a and MPO, C5a and Cp in the patient group were statistically significant ( r=0.663, P<0.001;r=0.792, P<0.001;r=0.637, P<0.001, respectively).No significant correlation was found in MPO-ANCA and any of these indexes.MPO-ANCA had a positive association with the total BVAS, the kidney BVAS, and the lung BVAS ( r=0.247, P=0.004;r=0.339,P<0.001 and r=0.191, P=0.028, respec-tively) .p-ANCA had a positive correlation with the kidney BVAS ( r=0.208, P=0.017) while C5a had a negative correlation with the kidney BVAS ( r=-0.207, P=0.018) . Conclusion The levels of MPO, Cp and C5a increased significantly in the peripheral blood of MPO-AAV patients in active phase.The complex interactions among MPO, Cp, C5a and ANCA might influence the clinical damage in MPO-AAV.Notablely, the influence from MPO-ANCA might be most obvious while C5a might affect renal damage more markedly.

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.

Objective To analyze the clinical characteristics of vasculitis associated with antineutrophil cytoplasmic antibody against myeloperoxidase (MPO-ANCA),and to investigate preliminarily the relationship between MPO-ANCA and the clinical damages.Methods One hundred and thirty-two patients with primary antineutrophil cytoplasmic antibody (ANCA) associated vasculitis,which were diagnosed for the first time,were involved into this prospective study.All the patients had positive laboratory tests for peri-nuclear ANCA (p-ANCA) and MPO-ANCA.The characteristics of their clinical presentations were analyzed.The levels of p-ANCA and MPO-ANCA in the peripheral blood were detected and the relationship between the levels and the damages were explored.T-test and Spearman rank correlation analysis were used for statistical analysis.Results Of the 132 patients from 8 different clinical departments,128 (97.0％) were microscopic polyangiitis (MPA),3 (2.3％) were granulomatosis with polyangiitis (GPA),and 1 (0.7％) was eosinophilic granulomatosis with polyangiitis (EGPA).The mean age was (62±15) years old.The average time between onset of the disease and diagnosis was (10 ±18) months,and only 14 (10.6％) were diagnosed within one month.Among the major organ involvements,the occurrence of renal,lung,joint,heart,peripheral nerve,skin,and central nerve involvement was 72.0％(95 cases),67.4％(89 cases),26.5％(35 cases),19.7％ (26 cases),17.4％(23 cases),10.6％(14 cases) and 9.8％(13 cases),respectively.Lung was more susceptible to be involved among the aged in their early course [(66±11) years,(55±19) years,t=-3.478,P＜0.01; (6±10) months,(18±27) months,t=2.920,P＜0.01],and joint involvement was more common in the younger [(57±18) years vs (64±13) years,t=2.335,P＜0.05] patients.p-ANCA had no relationship with the disease activity or the range of organ involvements(r=0.013,P＞0.05; r=0.087,P＞0.05).MPO-ANCA had a positive association with disease activity but had no significant correlation with the range of organ involvements(r=0.258,P＜0.01; r=0.022,P＞0.05).Conclusion The MPO-ANCA associated vasculitis is not rare in our country.MPA is the most common vasculitis which mainly affects the aged population,and its diagnosis is often delayed due to the lack of characteristic clinical presentations.It is possible that MPO-ANCA may play a pathogenic role in vasculitis,and the various clinical manifestations might be related with the specificities of MPO-ANCA.

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.

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.

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.

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.

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.

Objective To investigate the change of circulating follicular helper T cells (cTfh) in patients with anti-neutrophil cytoplasmic myeloperoxidase antibody-associated vasculitis (MPO-AAV), and to analyze the relationship between cTfh and disease activity. Methods Thirty-eight untreated MPO-AAV patients (patient group) and thirty-eight healthy volunteers (control group) were enrolled in this study. cTfh and membrane expression of inducible co-stimulator(ICOS)and programmed cell death protein 1(PD-1) were detected by flow cytometry (FCM). Serum anti-neutrophil cytoplasmic myeloperoxidase antibody (MPO-ANCA) was measured by ELISA. Disease activity was evaluated by Birmingham vasculitis activity score (BVAS). Results Compared with those in control group, the proportions of cTfh, ICOS+Tfh and PD-1+Tfh cells in patient group were significantly higher [(25.9±3.8)％vs. (21.0±5.3)％, P<0.001;(1.8±0.8)％vs. (0.8±0.5)％, P<0.001 and (10.2±2.8)％vs. (8.2±2.2)％, P=0.001, respectively]. Meanwhile, the expression of ICOS and PD-1 on cTfh in patient group was markedly more intensive (59.6±10.0 vs.49.2±6.9, P<0.001 and 532.6±104.2 vs. 485.1±73.4, P=0.025, respectively). In patient group, the proportion of cTfh was positively correlated with the ratio of ICOS+Tfh, the expression of ICOS, the level of MPO-ANCA and BVAS (r=0.407, P=0.011; r=0.705, P<0.001; r=0.737, P<0.001 and r=0.663, P<0.001, respectively). The expression intensity of ICOS on cTfh was positively associated with ICOS+Tfh ratio, serum MPO-ANCA and BVAS (r=0.388, P=0.016; r=0.645, P<0.001 and r=0.653, P<0.001, respectively). Nevertheless, the expression of PD-1 on cTfh was only positively correlated with the ratio of PD-1+Tfh (r=0.473, P=0.003). Conclusions Enhanced cTfh in patients with MPO-AAV might produce MPO-ANCA, which is related to the aggravation of MPO-AAV. Thus, cTfh and its ICOS could be potentially targeted for the treatment of MPO-AAV.