The Clinical Characteristics Of Patients With Relapsing Polychondritis And Application Of New Inflammatory Markers

Objective:We aimed to explore the clinical characteristics of relapsing polychondritis(RP)patients,and investigated the effect of sex difference on clinical features of RP patients.The novel inflammatory markers C-reactive protein to albumin ratio(CAR),neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),monocyte to lymphocyte ratio(MLR),and albumin to fibrinogen ratio(AFR)could predict the activity status of autoimmune diseases.We assessed the correlation between these novel inflammatory markers and relapsing polychondritis disease activity index(RPDAI).Methods:The clinical materials and laboratory indexes of RP patients who were hospitalized between December 2005 and September 2019 at Peking Union Medical College Hospital(PUMCH)were collected retrospectively.The clinical features of overall RP patients and those overlapped with other diseases were described.After excluding the RP patients combined with other diseases,the remaining RP patients were grouped on the basis of sex.The effect of sex difference on organ involvement in RP patients was analyzed by multivariate logistic regression analysis.In the section of novel inflammatory markers,RP patients hospitalized between December 2015 and February 2019 at PUMCH were included.The exclusive criteria were that RP patients combined with other diseases,and those with incomplete laboratory tests,such as routine blood test,blood albumin,blood fibrinogen,hypersensitive C-reactive protein/C-reactive protein.The correlation between CAR,NLR,PLR,MLR,AFR and RPDAI was assessed by using multivariate linear regression analysis model.Results:There were 212 hospitalized RP patients between December 2005 and September 2019.The age distribution in 40-49 age group was the most common age of onset.During the disease course,the involvement of airway accounted for 75%,followed by fever(70.8%).There were 19 patients overlapped with other diseases.Among these,5 patients overlapped with granulomatosis with polyangiitis(GPA).2 patients overlapped with myelodysplastic syndrome(MDS),ankylosing spondylitis(AS),pulmonary tuberculosis and tumor respectively.After controlling the age of onset and the delay time of diagnosis,the ocular involvement was more frequent in RP patients associated with other diseases than those without the related diseases.After controlling the age of onset and the delay time of diagnosis,the probability of joint involvement in male RP patients was 0.357 times compared with that in female RP patients(p=0.003,95%CI 0.181-0.701).A total of 170 RP patients were included to explore the application of novel inflammatory markers in RP patients.CAR,NLR,PLR,erythrocyte sedimentation rate(ESR)and neutrophil counts in peripheral blood positively correlated with RPDAI.Blood albumin,lymphocyte count,hemoglobin(Hb)negatively correlated with RPDAI.After controlling the admission age and course of disease,the result revealed the CAR,NLR and PLR were correlated with RPDAI(R2=0.060,standardized regression coefficient ?=0.175,p=0.023;R2-0.098,standardized regression coefficient ?=0.265,p=0.001;R2=0.069,standardized regression coefficient ?=0.199,p=0.009).Conclusion:The age from 40-49 was the most common age of onset in RP patients.The Airway involvement was the most common manifestation throughout the course of disease.GPA is the most common co-morbidity of RP.After controlling the age of onset and the diagnosis delay,the ocular involvement was more frequent in RP patients associated with other diseases than those without the related diseases.In addition,the joint involvement was more common in female RP patients compared with male RP patients.After controlling the admission age and course of disease,the novel inflammatory markers CAR,NLR and PLR were correlated with RPDAI.Among these,the correlation between NLR and RPDAI was the strongest.Objective:We aimed to investigate renal injury characteristics in Chinese patients with systemic sclerosis(SSc)who had undergone renal biopsy.Methods:We retrospectively collected the medical records of patients with SSc who were hospitalized at PUMCH between January 1990 and August 2019 and were performed percutaneous renal biopsy simultaneously.We analyzed the clinical characteristics and pathological results of these patients.Results:We identified 25 patients who had undergone renal biopsy.Of these patients,10 had scleroderma renal crisis(SRC);one underwent renal biopsy twice(for diffuse mesangial proliferative glomerulonephritis and for SRC);two had antineutrophil cytoplasmic antibody(ANCA)associated glomerulonephritis;one had immunoglobulin M(IgM)nephropathy;one had minimal change nephropathy;seven had lupus nephritis(LN).Two of seven patients underwent renal biopsy twice.In detail,in one patient,the pathological finding of renal biopsy was ?LN for the first time.The pathological finding of renal biopsy was ?LN combined with V LN for the second time.In another patient,the pathological finding of renal biopsy was ? LN for the first time.The pathological finding of renal biopsy was ? LN combined with V LN for the second time;one had SRC with comorbid LN;and two had drug-related kidney injury(caused by aristolochic acid in one and D-penicillamine in the other).Acute tubular necrosis was observed in the patient taking oral aristolochic acid,while minimal change nephropathy was observed in the patient with D-penicillamine-induced renal injury.The thrombotic microangiopathy(TMA)was observed in all patients with SRC.An“onion skin”appearance was present,in combination with luminal stenosis,endothelial edema and proliferation,intimal mucoid change and edema,erythrocyte fragments within the arterial vessel wall,interlobular artery fibrinoid necrosis,ischemic glomeruli,hyalinosis in small arteries,and thrombi.The proliferation of arteriole elastic fibers,which exhibited an“onion skin" concentric appearance with luminal stenosis,was the most common manifestation in patients with SRC.Conclusions We observed various types of renal histopathologic changes in patients with SSc,such as SRC,diffuse mesangial proliferative glomerulonephritis,ANCA-associated glomerulonephritis,IgM nephropathy,minimal change nephropathy,LN,SRC with comorbid LN,drug induced renal lesions(aristolochic acid and D-penicillamine).The changes in the pathologic type of LN were observed in the different course of disease.Rheumatologists in Eastern countries should be aware of aristolochic acid nephropathy.What was particularly noteworthy was that SRC was the most commonly encountered renal damage in patients with SSc.The histopathological manifestation of TMA was observed in all patients with SRC.Among these,the proliferation of arteriole elastic fibers,which exhibited an“onion skin”concentric appearance with luminal stenosis,was the most common one.The abovementioned various types of renal injuries in SSc patients can cause symptoms similar to those of SRC.Distinguishing between SRC and the other types of renal lesions is critical because of the distinct management approaches.We recommend biopsy for patients undergoing treatment for SRC who have persistent renal injury with proteinuria,regardless of hematuria.Objective:We aimed to preliminarily explore the pathogenesis of angiogenesis in patients with systemic sclerosis(SSc).In addition,the potential role of CD4+CXCR5-PD-1+peripheral helper T(Tph)cell and CD4+CXCR5+CD25+Foxp3+follicular regulatory T(Tfr)cell in the abnormal immunity of SSc patients was also investigated.Methods:The SSc patients that were hospitalized and visited the outpatient clinics between April 2019 and December 2019 were included in the study.The expression of junctional adhesion molecule A(JAMA)on circulating endothelial cells(CECs),Tph cell,the markers of Tph cell,intracellular cytokines of Tph cell,and Tfr cell were measured by flow cytometry.The differences were compared between healthy control(HC)and SSc patients.If there were the statistical differences,the patients were divided into groups based on the organ involvement.The correlation analysis with other cell subsets and laboratory indexes were performed.Results:The ratio of CECs,apoptotic CECs,activated CECs between HC and SSc patients was not significantly different.There were also no differences in JAMA expression on surface of mononuclear cells(RNs),CECs,apoptotic CECs,and activated CECs between HC and SSc patients.The expression of Tph cells were detected in 62 SSc patients and 46 HC.Only 3 patients with SSc were not treated with glucocorticoid and immunosuppressant before.Compared with HC,the Tph cell numbers was obviously increased(3.52±1.27 vs 3.04±1.04,p=0.04).The Tph cell numbers were particularly higher in SSc patients without the treatment of glucocorticoid and immunosuppressant before,or had stopped glucocorticoid and immunosuppressants for more than 3 months(4.40±1.33%vs 3.36+1.20%,p=0.02).The expression of chemokine receptor(CCR)2?CD25,CD38?CD69?T cell Ig and ITIM domain(TIGIT)?Inducible T cell costimulatory(ICOS)?CCR7 and transcription factor T-bet by Tph cell were not significantly different between HC and SSc patients.The CD127 mean fluorescence intensity(MFI)on Tph cell was lower in SSc patients than HC(1734.00±325.50 vs 1510.00±307.00,p=0.03).In terms of cytokine secretion of Tph cells,interleukin-21(IL-21)expression did not differ(11.30±2.90 vs 12.67±2.88,p=0.46).However,the tumor necrosis factor-?(TNF-?)expression were lower in SSc patients than HC(48.35±10.16 vs 34.14±12.94,p=0.03).The expression of circulating Tph cell in SSc patients was positively correlated with absolute value of basophils in peripheral blood(r=0.2581,p=0.0429)?platelet(PLT)(r=0.3605,p=0.0040)?red cell volume distributing width-standard deviation(RDW-SD)(r=0.2695,p=0.0373)?follicular helper T(Tfh)cells(r=0.374,p=0.002).No associations between Tph cell and Medsger disease severity score?European Scleroderma Study Group activity index(EScSG-AI)?revised European Scleroderma Trials and Research Group Activity Index(EUSTAR-AI)?plasma cell?Naive B cell?regulatory B cell,memory B cell?plasmablast?CD19+CD11c+B cell?CD19+CD11c+CD21-T-bet+atypical B cell were found.The circulating Tfr/Tfh ratios of 16 SSc patients and 9 HC were detected.Although not significantly different,Tfr/Tfh ratio in SSc patients tended to be higher than HC(0.012±0.01 vs 0.008±0.003,P=0.11).Conclusion:The expression of JAMA on circulating MNs was not different between SSc patients and HC.The circulating Tph numbers were higher in SSc patients,especially in patients without the treatment of glucocorticoid and immunosuppressant before,or had stopped glucocorticoid and immunosuppressants for more than 3 months.In contrast to HC,the CD127 MFI on Tph cell and TNF-? expression of Tph cell were lower in patients with SSc.The expression of circulating Tph cell in SSc patients was positively correlated with absolute value of basophils in peripheral blood?PLT number?RDW-SD?Tfh number.No correlation between Tph cell and B cell subsets were found in SSc patients.Compared with HC,SSc patients had the tendency of increasing Tfr/Tfh ratio in peripheral blood.