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Study of the expression of peripheral blood lymphocyte P-glycoprotein in rheumatoid arthritis patients and reversing P-glycoprotein-induced drug resistance

Xiangcong ZHAO ; Caihong WANG ; Jing LUO ; Xuefei LI ; Xiaojian LIU ; Xiaofeng LI

Chinese Journal of Rheumatology.2013;17(10):672-676. doi:10.3760/cma.j.issn.1007-7480.2013.10.006

Objective To study the expression of peripheral blood lymphocyte P-glycoprotein(P-gp)and related impact factors in rheumatoid arthritis(RA)patients,and explore whether the periodic combination of methotrexate(MTX)or leflunomide(LEF)with cyclophosphamide(CTX)could reverse P-gpinduced drug resistance.Methods This study was a cross-sectional study.Forty-two RA patients were enrolled(15 cases in the primary untreatment group,while 27 cases in the treatment group).In the treatment group,patients were divided into the improvement group(12 patients)and the refractory group(15 patients)respectively according to their disease activity scores(DAS 28).According to the medication used,42 patients were divided into 3 groups:the monotherapy group(MTX or LEF),the MTX+LEF combination treatment group and MTX or LEF+CTX treatment group.The expression of peripheral blood lymphocyte P-gp in each group was detected by flow cytometry.T test,ANOVA,LSD test,Bonferroni test,x2 test and Pearson correlation analysis were used for statistical analysis with software 13.0.Results ① Mean relative fluore scence intensity(RFI)of P-gp was 2.0±0.7,2.9±1.0,3.5±1.4,5.0±2.0 respectively in healthy control group,the primary untreatment group,the improvement group and the refractory group,the difference was significant(F=7.955,P＜0.01).in multiple comparisons,the fluorescence intensity was higher in the primary untrea-tment group as compared to the healthy group,but the difference was not statistically significant(P=0.137);however,it was significantly higher in the refractory group as compared to the improvement group(P=0.013).② There was no correlation between the expression of P-gp in RA patients and sex,age of onset,disease duration or positive rate of RF.But the expression of P-gp was significantly correlated with ESR and DAS28(r=0.447,P=0.002;r=0.398,P=0.012).③ RFI of the P-gp group was 5.1±2.2,6.0±1.2,3.4±1.1 respectively in monotherapy group,MTX+LEF group and MTX/LEF+ CTX group(P＜0.05).The expression of P-gp was significantly lower in the MTX/LEF+CTX group as compared to the monotherapy group(P＜0.05),but higher in the MTX+LEF group(P＞0.05).Conclusion The expression of peripheral blood lymphocyte P-gp in RA is correlated with disease activity.The loss of efficacy in DMARDs is due to the enhanced expression of P-gp.Combination of methotrexate or leflunomide with cyclo-phosphamide reverses P-glycoproteininduced drug resistance.

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Enhance-flow and spectral Doppler study on the hemodynamics of ophthalmic artery in hyperuricemia

Ling LI ; Jingguo ZHOU ; Peng GU ; Jia CHEN ; Yufeng QING

Chinese Journal of Rheumatology.2013;17(10):677-680. doi:10.3760/cma.j.issn.1007-7480.2013.10.007

Objective To study the inner diameter and hemodynamics of ophthalmic artery(OA)and central retinal artery(CRA)in hyperuricemia by Enhance-flow(eFlow)imaging and spectral Doppler.Methods One hundred and one patients with hyperuricemia and 30 volunteers were selected,the inner diameter in eFlow imaging and the peak systolic velocities(PSV),the end diastolic velocities(EDV),the resistive index(RI)were measured,and pulsatility index(PI)of OA and CRA were measured by spectral Doppler.The 101 patients were divided into two groups according to the time of diagnosing hyperuricemia,one group had a diagnosis of hyperuricemia for more than five years and the other had such a diagnosis for less than five years.The data were compared by t-test.Then,the patients were further divided into a group of hyperuricemia combined with hypertension and the other without hypertension.The differences between the experimental group and the group of volunteers were carried out by One-way ANOVA,the comparison between two groups were analyzed with SNK.Results The RI(0.68±0.09)and PI(1.3±0.4)of OA in patients who were diagnosed as hyperuricemia for more than 5 years was higher[RI:0.63±0.09,PI:1.1±0.3(t=3.504,P=0.001 ;t=3.164,P=0.002)],the EDV[(6±3)cm/s]of OA was lower than those patients with a diagnosis of hyperuricemia for less than 5 years[(8±5)cm/s,t=1.988,P=0.049].The PSV[(11.5±3.5)cm/s]and EDV[(3.7±1.1)cm/s]of CRA in hyperuricemia combination hypertension group was lower,and the RI (0.88±1.40)was higher than hyperuricemia without hypertension group[PSV:(13.5±4.0)cm/s,EDV:(4.1±1.2)cm/s,RI:0.67±0.08].Conclusion By eFlow and spectral Doppler,we have found that hyperu-ricemia could accelerate OA and CRA atherosclerosis.The eFlow and spectral Doppler are valuable methods to study the hemodynamics in ophthalmic artery of patients with hyperuricemia.

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Clinical analysis of peripheral neuropathy in patients with systemic lupus erythematosus

Xianbin WANG ; Huiying LI ; Dong XU ; Yan XU ; Fengchun ZHANG ; Xiaofeng ZENG

Chinese Journal of Rheumatology.2013;17(11):738-742. doi:10.3760/cma.j.issn.1007-7480.2013.11.005

Objective To investigate the frequence and clinical characteristics of peripheral neuropathy (PN) of patients with systemic lupus erythematosus (SLE) in China.Methods The data of 67 consecutive PN related with SLE (SLE-PN) patients admitted to Peking Union Medical College Hospital (PUMCH) during January 1995 to August 2011 were retrospectively analyzed.At the same time,a total of 201 cases were randomly selected as controls from 4447 SLE patients without SLE-PN in PUMCH during the same period.Chi-square test,t test and Mann-Whitney test were used for statistical analysis.Results The prevalence of SLE-PN in SLE patients was 1.5％(67/4514).Seventy-two cases of PN were discovered in 67 patients.Polyneuropathy was the most frequent presentation and was diagnosed in 45 cases(62.5％),mononeuropathy in 9 cases (12.5％),myasthenia gravis in 8 cases (11.1％),cranial neuropathy in 7 cases (9.7％),autonomic disorder in 2 cases (2.8％) and acute inflammatory demyelinating polyradiculoneuropathy in 1 case (1.4％).No plexopathy was diagnosed.No symptoms were observed in 5 cases (6.9％) PN.There were differences between SLE patients with and without SLE-PN in age[(37±14) years vs (32±14) years,P＜0.05],fever(65.7％ vs 47.8％,P＜0.05),myositis (17.9％ vs 5.0％,P＜0.01),skin and mucous involvement of skin and mucous (80.6％ vs 59.7％,P＜0.01),central nervous system involvement (38.8％ vs 19.9％,P＜0.01),gastrointestinal involvement (6.0％ vs 18.4％,P＜0.05),anti-Sm antibody positivity (34.4％ vs 18.6％,P＜0.05),anti-RNP antibody positivity (46.9％ vs 29.9％,P＜0.05),elevation of IgG (52.4％ vs 30.1％,P＜0.01),and SLEDAI score [12.0(9.0) vs 9.5(10.8),P＜0.05].Conclusion SLE-PN is not rare in patients with SLE.SLE patients with peripheral neuropathy tend to have more active disease.Multidisciplinary collaboration and comprehensive treatment can help to relieve pain and improve the quality of life.

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Analysis of the incidence of hospitalized children with Henoch-Sch(o)nlein purpura and Henoch-Sch(o)nlein purpura nephritis

Hong LIU ; Rui FU ; Douxing HAN ; Baojin HU ; Weimin ZHENG ; Yuhui HUANG

Chinese Journal of Rheumatology.2013;17(11):756-759. doi:10.3760/cma.j.issn.1007-7480.2013.11.008

Objective To analyze the incidence of hospitalized children with Henoch-Sch(o)nle in purpura (HSP) and Henoch-Sch(o)nlein purpura nephritis (HSPN) from 2009 to 2012,and to characterize the epidemiology of HSP and HSPN in Jiangxi province.Methods Inpatients of Jiangxi Children's Hospital with the diagnosis of HSP or HSPN were recruited during 2009 to 2012.The basic messages in the home page of medical records,such as the admission year,sex,age,area coming from were collected.Chi-square test was used for statistical analysis.Results A total of 2516 HSP pediatric patients were included in this study.Of whom,412 cases were diagnosed in 2009,568 cases in 2010,750 cases in 2011,786 cases in 2012.Among them,renal damage as the presenting symptom in 110 cases in 2009,148 cases in 2010,198 cases in 2011,and 196 cases in 2012.The average incidence of HSPN was 25.91％ (652/2516).The morbidity of HSPN were similar in different admission years (x2=0.62,P＞0.05).In HSP patients,the ratio between male and female was 1.59∶1; the peak age was 4 to 9 year-old (65.50％,1648/2516).The morbidity of HSPN was similar in both girls and boy patients group (x2=0.14,P＞0.05).The morbidity of HSPN was 18.76％ (163/869) in patients younger than 6 years old,which was lower than 26.85％(359/1337) in patients between age 6 to 11 years old,and the morbidity of HSPN was 41.94％ (130/310) in patients older than 11years old,the difference was significant (x2=65.24,P＜0.01).The morbidity of HSP in the month of year was different,the peak time was between October and December,which as 40.74％(1025/2516).The morbidity of HSPN was 30.23％(208/688) during January to March,higher than in other period of the year (x2=9.87,P＜0.05).In the last four years,there were 824(32.75％) hospitalized patients of HSP in Nanchang district,1692 cases (67.25％) in other areas in Jiangxi province.The morbidity of HSPN in Nanchang district was 17.35％ (143/824),compared with the average level 25.91％(652/2516),the difference was significant (x2=25.08,P＜0.01).Conclusion The number of children diagnosed with HSP is progressively increased from 2009 to 2012 in Jiangxi province.The peak period for HSP is between October and December,and the peak age is 4 to 9 year-old.The incidence of HSPN between January to March group is higher than in other periodof the year.The morbidity of HSPN is increased with age.

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The role of vitamin D in bone metabolism of ankylosing spondylitis

Jianli XIE ; Ping WEI ; Junxiang WANG ; Hanying CHEN ; Jinghong MENG

Chinese Journal of Rheumatology.2013;17(11):771-774. doi:10.3760/cma.j.issn.1007-7480.2013.11.012

Objective The goal of this study was to investigate the correlation between the level of serum vitamin D and bone metabolism and disease activity in ankylosing spondylitis(AS) patients,and thus to explore the role of vitamin D in bone metabolism in AS patients.Methods The serum levels of BALP,TRACP-5b,25-(OH)D3 and blood lymphocytes VDR of 80 AS patients were measured by enzyme-linked immunosorbent assay (ELISA) and compared with those of the control group.Bone mineral density (BMD)was measured by dual-energy X-ray absorptiometry (DEXA).The ESR and CRP level of AS patients were also measured.The correlation between those parameters was analyzed and evaluated.Patients were divided into normal,insufficient and deficient subgroups according to the serum 25-(OH)D3 levels for further comparison.Indepondent saimple t test,t'test andx2 test were used for statistical analysis.Results The 25-(OH)D3 of AS patients [(11.9±2.7) μg/L] was significantly lower than that of the control groups [(22.3±7.9) μg/L] (P＜0.05),while the serum levels of BALP [(3.9±2.7) μg/L] and TRACP-5b [(46±25) ng/L] of AS patients were significantly higher than those of the control group [(2.4±1.0) μg/L] (P＜0.05).According to linear correlation analysis,25-(OH)D3 was negatively correlated with CRP (r=0.324,P=0.003).The ESR,BALP,TRACP-5b in the deficient subgroup were higher than those in the normal and insufficient subgroups(P＜0.05).Conclusion The plasma 25-(OH)D3 may decrease in AS patients,and this may activate bone metabolism,results in increased morbidity of osteoporo-sis,and negatively affect disease activity.

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Relationship between macrophage migration inhibitory factor-173G/C polymorphism and susceptibility to gout in Chinese male population

Ziyun ZHUANG ; Bin LIU ; Ruimei CHUAI ; Longqiang XU ; Changgui LI ; Shiguo LIU

Chinese Journal of Rheumatology.2013;17(10):692-695. doi:10.3760/cma.j.issn.1007-7480.2013.10.011

Objective To explore gene polymorphism of the G/C genotype of-173G/C(rs755622)in the promoter of macrophage migration inhibitory factor(MIF)gene in male population,and thus to investigate the relationship between gene polymorphism of MIF and gout.Methods A total of 380 gout patients and 378 healthy controls were enrolled.The possible association between the polymorphism of MIF-173G/C and gout in Chinese were investigated and genotype frequencies and allelic frequencies were analyzed by polymerase chain reaction with sequence-specific primers(PCR-SSP)method.Hardy-Weinberg was used to verify the representativeness of the samples.Comparisons between the groups were performed with x2 test.The gene polymorphism of MIF and gout was performed by t test.Results The frequencies of GG,GC,CC genotypes were 62.1％(236 cases),34.2％(130 cases)and 3.7％(14 cases),respectively among gout patients,while they were 66.5％(252 cases),29.8％(113 cases)and 3.7％(14 cases),respectively among the controls.There was no statistical difference in MIF-173G/C genotype frequencies between gout patients and controls(x2=1.713,P=0.425).The allele frequencies of G and C in gout cases were 79.2％(602 cases)and 20.8％(158cases),while the controls were 81.4％(617 cases)and 18.6％(141 cases),and no significant difference between them could be found(x2=1.148,P=0.302).Combine GG and GC of gout into GG+GC,the association analysis of the two groups showed that,mean age,leves of glucose,TG,TC,BUN,Cr and UA of the GG+GC group and the CC group were(51±13)and(50±15)t=0.369,P=0.712;(7.1±8.8)and(6.1±1.2)mmol/L,t=0.352,P=0.725;(2.3±1.6)and(2.9±3.4)mmol/L,t=-1.207,P=0.228;(5.3±1.2)and(5.7±1.4)mmol/L,t=-1.207,P=0.228;(5.8±2.9)and(6.2±2.2)mmol/L,t=-0.513,P=0.608;(92±52)and(84±17)μmol/L,t=0.537,P=0.592;(472±103)vs(557±154)μmol/L,t=-2.949,P=0.03 respectively;no significant difference was found in the two group.Moreover,no association between MIF-173G/C genotypes and risk factors for gout were detected in gout cases by t-test.Conclusion Results of the present study suggest that the G/C genotype of-173G/C in the promoter of MIF gene is not associated with gout in male population.

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Association of TLR4 gene polymorphisms with susceptibility to primary gouty arthritis in Chinese Han population

Yufeng QING ; Jingguo ZHOU ; Quanbo ZHANG ; Min LI ; Cuiping HUANG ; Ling YING

Chinese Journal of Rheumatology.2013;17(11):724-728. doi:10.3760/cma.j.issn.1007-7480.2013.11.002

Objective To investigate the association of TLR4 gene polymorphisms with susceptibility to primary gouty arthritis (GA) in Chinese Han population.Methods A total of 459 patients with GA and 459 healthy control subjects were enrolled into this study.All the genotyping assays of TLR4 gene polymorphisms loci [rs4986790 (Asp299Gly),rs4986791 (Thr399Ile),rs2 1 49356T＞G] were measured using TaqMan probes that specifically target the alternate alleles.Results All the subjects were found to be homozygous for the wild-type TLR4 alleles (Asp/Asp,Thr/Thr) on TLR4 Asp299Gly and Thr399Ile genotyping.There was no significant deviation from HWE both in GA and controlsin the rs2149356 (x2=0.778,1.295; P＞0.05,respectively).Significant differences were observed between the GA and control groups with respect to genotype and allele frequencies of TLR4 gene rs2149356 (x2=16.23,17.08; P＜0.01,respectively),and TT genotype was the risk factor for gout (adjusted OR=2.09).Conclusion The TLR4 gene rs2149356 SNP may be associated with GA susceptibility,and TT genotype may be the risk factor for developing gout.

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The study on the expression of interleukin-17 and receptor activator of nuclear factors κB-ligand in serum of patients with ankylosing spondylitis

Xiujuan LI ; Shengqi HUANG ; Ani WANG ; Hui ZHENG ; Shiying LI ; Weiguang CHEN ; Feng WEI

Chinese Journal of Rheumatology.2013;17(11):769-771. doi:10.3760/cma.j.issn.1007-7480.2013.11.011

Objective To investigate the role and value of interleukin (IL)-17,receptor activator of nuclear factors κB-ligand (RANKL),osteoprotegerin (OPG) in the pathogenesis of AS by detecting the expression of IL-17,RANKL,OPG.Methods IL-17,RANKL,OPG in 44 AS and 15 healthy controls were measured by ELISA.HLA-B27 was measured by flow cytometry.T-test,Spearman's correlation analysis were used for statisical analysis.Results ① Serum IL-17 [(45±12) pg/ml],RANKL [(354±96) pg/ml] levels and RANKL/OPG [(6.5±3.4) pg/ml] ratio were significantly higher in AS patients than those in normal controls (t=11.18,P＜0.05; t=18.66,P＜0.05; t=15.48,P＜0.05),and the serum RANKL levels was higher in AS patients in middle and late period than that in AS patients in early stage (t=47.02,P＜0.05).The serum OPG levels was higher in AS patients in middle and late period than that in AS patients in early stage (t=15.48,P＜0.05).② There were positive linea correletion,respectively,between the serum levels of IL-17 and RANKL (r=0.532,P=O.021),and between serum levels of IL-17 and disease activities of BASDAI (r=0.625,P=0.023),between serum levels of RAN KL and disease activities of BASDAI (r=0.431,P=0.016).Conclusion The surem levels of IL-17 and RANKL are increased in AS patient.

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Multiple myeloma presented as polyart hritis: case reports and literature review

Yanying LIU ; Li ZHANG ; Aichun LIU ; Hua YE ; Yuhui LI ; Zhanguo LI

Chinese Journal of Rheumatology.2014;18(3):195-198. doi:10.3760/cma.j.issn.1007-7480.2014.03.012

Objective We reported 5 unusual cases of multiple myeloma (MM) initially presented as polyarthritis.Special attention should be paid to this very unusual scenario.Methods Five cases who presented initially as polyarthritis and finally diagnosed as MM were administered to Peking University People's Hospital and 11 cases from literature were reported.The clinical symptoms and laboratory parameters were analyzed respectively.Results The primarily affected joints were small joints,such as metacarpophalangeal joints,proximal interphalangeal joint,metatarsophalangeal and temporomandibular joints,but large joints such as wrists,elbows,shoulders,knees,ankle joints could be involved,too.Fourteen of 16 patients were misdiagnosed as rheumatoid arthritis (RA).Renal dysfunction presenting as high level of serum creatinine or proteinuria was detected in 14 cases.Laboratory tests showed elevated erythrocyte sedimentation rate or C reactive protein level in 13 cases.Anemia was detected in 9 cases.Hypercalcemia was detected in half of the patients.Hyperglobu-linemia was detected in 6 cases.The serum level of free M-protein was markedly elevated in 14 cases.Auto-antibodies were negative,except that rheumatoid factor was positive in 1 case.Conclusion It is important to pay attention to the clinical pictures presented as polyarthritis with negative autoantibodies,and associated with renal dysfunction,anemia and hypergammaglobulinemia.MM is important in the differential diagnosis.

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Clinical characteristics of patients with polyarteritis nodosa

Xianbin WANG ; Dong XU

Chinese Journal of Rheumatology.2014;18(1):34-38. doi:10.3760/cma.j.issn.1007-7480.2014.01.008

Objective To investigate the clinical characteristics of patients with polyarteritis nodosa (PAN),and to improve the understanding of the disease.Methods The data of 65 consecutive PAN patients admitted to Peking Union Medical College Hospital from October 2001 to March 2013 were analyzed.Patients were divided into two groups based on hapatitis B surface antigen (HBsAg) status.Chi-square test,Fisher exact probability,t test and Mann-Whitney test were used for statistical analysis.Results The male/female ratio of patients with PAN was 1.3/1,and the average age was (37.6±1.6) years old.Fever (in 40 cases,62％) was the most frequent manifestation.Skin was involved in 51 cases (79％),urologic involvement in 44 cases (68％),peripheral nervous system involvement in 22 cases (34％) and gastrointestinal involvement in 21 cases (32％).Forty-six (71％) patients had high-sensitivity C reactive protein (hs-CRP) elevation and 11 (17％) patients had eosinophil count elevation.The most common vascular involvements were limb arteries in 22 cases (34％),renal artery in 19 cases (29％),and gastrointestinal artery in 17 cases (26％).Patients with negative HBsAg had more frequent arthralgia or arthritis(41％ vs 9％,x2=4.00,P＜0.05),more indicators of poor prognosis (30％ vs 0,P＜0.05) and more glucocorticoid pulse therapy (30％ vs 0,P＜0.05) when compared with patients with positive HBsAg.Conclusion Clinical manifestations of PAN are complex.Young patients with fever of unknown origin,rash,weight loss,myalgias,accompanied by symptoms of multi-organ damage including urologic,peripheral nervous system,gastrointestinal involvement and negative autoantibodies should be highly suspected for the diagnosis of PAN.For the treatment of patients with positive HBsAg,special attention should be paid to maintain the delicate balance between controlling the organ damage caused by PAN and prevention of hepatitis B virus (HBV) infection reactivation.

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