Aca 2013 Abstract Export Plenary Session: Plenary Session 1: Novel aspect of therapeutics of autoimmune diseases



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Data shown in n (%). OR = odds ratio; 95% CI = 95% confidence interval; genotype analyses in codominant genetic model for association were used by Logistic Regression with SPSS software (version 13.0, SPSS Inc.).
P1-044 THE TRAF1/C5 (RS3761847) AND THE RISK OF RHEUMATOID ARTHRITIS: A CASE-CONTROL STUDY INDIVIDUALLY MATHCED ON SEX
H. Li1, Y. Hu2, T. Zhang1, Y. Liu3, X. Su1, Y. Zhu1, Y. Wang3, T. Yang3, M. Li3, Q. Luo1, Y. Cheng1, Q. Zou3


1Department of Oncology, Chengdu Military General Hospital, Chengdu, China
2Department of traditional Chinese medicine, Chengdu Military General Hospital, Chengdu, China
3Department of Immunology, Chengdu Medical College, Chengdu, China

Background and aims: A SNP (rs3761847) in TRAF1-C5 locus on chromosome 9 was found to be an increased risk for anti-CCP-positive rheumatoid arthritis (RA) by the genome-wide study in the North American Rheumatoid Arthritis Consortium (NARAC) and the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA)[1]. Here, we investigated whether the susceptibility loci in Caucasian was associated with RA in Han Chinese population. Methods: 190 RA patients and 190 healthy controls among Chongqing city residents were evaluated in this study. Since RA was the sole disease for which the sex-differentiated analysis generated a strong signal due to different genetic effects in males and females, a single healthy control was matched with each case on the basis of sex, age and ethnicity to exclude age and sex bias. rs3761847 was genotyped in 380 subjects by Genotype-specific PCR. Results: Allele and genotype frequencies for the rs3761847 were in HWE in both the patient and the control populations. The minor G allele frequencies for RA case group did not differ significantly from those in the control group (43.7% versus 56.3%, P = 0.31; resulting OR = 0.86; 95% CI [0.65, 1.15], shown in the Table). The difference in the frequency of the GG genotype between patients and controls failed to reach statistical significance (15.8% versus 21.3%, P = 0.24; OR = 0.69; 95% CI [0.38, 1.28]). Conclusions: No evidence of the association between rs3761847 and RA was observed in our individually matched case-control study.

Acknowledgments: This work was supported by grants from the National Natural Science Foundation of China (No. 81072455), The Basic Research Program of Sichuan Province of China (No. 2012JY0031), Research Fund of Chengdu Military General Hospital (No.2011YG-B02 and No. 2013YG-A004), and Key Project of Chengdu Military Region during the 12th five-year plan period (No.A12003).
Table: association anlysis of rs3761847

allele/genotypes

controls no.(%)

cases no. (%)

OR

95%CI

P

A

198 (52.7)

213 (56.3)

1(reference)

-

-

G

178 (47.3)

165 (43.7)

0.86

0.65-1.15

0.31

AA

50 (26.6)

54 (28.6)

1(reference)

-

-

AG

98 (52.1)

105 (55.6)

0.99

0.62-1.59

0.97

GG

40 (21.3)

30 (15.8)

0.69

0.38-1.28

0.24

Data shown in n (%).OR = odds ratio; 95% CI = 95% confidence interval; Allele analysis for association were used by Pearson Chi-Square test and genotype analyses for association were used by Logistic Regression with SPSS software (version 13.0, SPSS Inc.).

1. Plenge RM, Seielstad M, Padyukov L, Lee AT, Remmers EF, Ding B, Liew A, Khalili H, Chandrasekaran A, Davies LR et al: TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study. N Engl J Med 2007, 357(12):1199-1209.


P1-045 ASSOCIATION OF IL-1F7 GENES WITH SUSCEPTIBILITY TO RHEUMATOID ARTHRITIS IN HAN CHINESE POPULATION
X. Zhang1, C. Li1, R. Mu1, Y. Zuo1, Y. Du1, X. Wu1, X. Lu2, R. Li1, J. He1, X. Liu1, F. Yin3, J. Guo1, Z. Li1


1The department of Rheumatology and Immunology, People's Hospital Peking University health science center, Beijing, China
2Department of Rheumatology, Xuanwu Hospital, Beijing, China
3The department of Rheumatology and Immunology, The First Affillated Hospital Baotou Medical College, Baotou, China

Background IL-37 is a natural inhibitor of inflammatory and immune responses and IL1F7 polymorphisms have been found to correlated with inflammatory diseases. This study was undertaken to investigate the role for genetic variants in IL-37 in RA susceptibility.

Methods Genotypes for five selected single-nucleotide polymorphisms (SNPs) in IL1F7 genes (rs 2723186, rs3811046, rs4241122, rs4364030, rs4392270) were determined by TaqManR Allelic Discrimination in Han Chinese population (727 RA cases and 610 healthy controls). Association analyses were performed on the whole data set and on RA subsets based on the status of anti-cyclic citrullinated peptide antibody. Association statistics were calculated by age and sex adjusted logistic regression.

Results No significant differences of distribution of alleles and genotypes were observed between case and control groups (P>0.05). The haplotype analysis showed that IL-1F7 genes were not significantly associated with susceptibility to RA.

Conclusions No significant correlation between RA susceptibility among the Han Chinese population and IL-1F7 genes is observed.

Table 1 Analysis of 5 SNPs in the IL-1F7 region in a Chinese rheumatoid arthritis population.



SNP

Allele

Cases




Controls




2 vs 1




Minor/Major

N

2/1

11

n (%)


12

n (%)


22

n (%)


MAF




N

2/1

11

n (%)


12

n (%)


22

n (%)


MAF




OR (95% CI)

p Value

rs2723186

A/G

687

197/1177

503

(73.2)


171

(24.9)


13

(1.9)


0.14




581

179/983

408

(70.3)


167

(28.7)


6

(1.0)


0.15




1.088

(0.874-1.355)



0.466

rs3811046

G/T

690

278/1102

440

(63.8)


222

(32.2)


28

(4.0)


0.20




603

244/1206

407

(67.5)


178

(29.5)


18

(3.0)


0.19




1.106

(0.909-1.345)



0.319

rs4241122

G/A

340

136/680

215

(63.2)


114

(33.5)


11

(3.2)


0.20




402

202/804

211

(52.8)


180

(44.8)


11

(2.7)


0.25




1.342

(1.049-1.717)



0.021*

rs4364030

G/C

346

341/692

94

(27.2)


163

(47.1)


89

(25.7)


0.49




430

436/860

101

(23.5)


222

(51.6)


107

(24.9)


0.51




1.058

(0.866-1.293)



0.610

rs4392270

A/G

349

91/607

262

(75.1)


83

(23.8)


4

(1.1)


0.13




407

110/814

302

(74.2)


100

(24.6)


5

(1.2)


0.14




0.957

(0.710-1.289)



0.820

1, major (common) allele; 2, minor (rare) allele.



* After Bonferronl correction, P value is not considered significant.
Poster Session: Session 1: Hormones: vitamin D, prolactin

P1-046 EFFECT OF VITAMIN D ON THE NUMBER AND FUNCTION OF THELPER 17 CELLS (CD4+IL-17A+) IN SLE PATIENTS WITH HIPOVITAMIN D
C.S. Wahono1, D. Soelistyoningsih2, K. Handono3, H. Kalim1, A.T. Endarti4


1Internal Medicine Faculty of Medicine, Brawijaya University, Malang, Indonesia
2Laboratory of Biomedical Science Faculty of Medicine, Brawijaya University, Malang, Indonesia
3Clinical Pathology Faculty of Medicine, Brawijaya University, Malang, Indonesia
4Parasitology Faculty of Medicine, Brawijaya University, Malang, Indonesia

Objective: To determine the effect of vitamin D [1,25 (OH) 2D3] in the number and function of Th17 cells (CD4+IL-17A+) in SLE patients with hipovitamin D.

Methods: CD4+ T lymphocytes from PBMCs of 5 SLE patients with hipovitamin D were cultured using RPMI 1640, PMA, ionomycin, Golgiplug, 10% heat-inactivated FCS, penicillin (100 IU/mL), and streptomycin (100 IU/mL). After stimulation with 10 ng/mL IL-6, 5 ng/mL TGF-β1, 10 µg/mL anti-IFN-γ, and 10 µg/mL anti-IL-4, and treated with various doses of 1,25 (OH) 2D3 ( P0: 0 M, P1:10-9M, P2: 10* 8 M, P3: 10-7 M), we analysed the the number and function of Th17 cells. The number (percentage) of Th17 cells was measured by flowcytometry, while Th17 cell function is measured by the levels of IL-17A expression using ELISA method.

Results: Compared with P0 (17:07 ± 2.99%), the mean percentage of Th17 cells in P1 (8:39 ± 3:29%; p = 0.043) and P2 (7:17 ± 3.81%; p = 0.038) were significantly lower. Similarly, the levels of IL-17A, in P1 (25.90 ± 11.90 pg/ml; p = 0.024) and P2 (15.75 ± 1.22 pg/ml; p = 0.047) were significantly lower than P0 (59.18 ± 26.95 pg/ml).

Conclusion: Administration of vitamin D [1,25 (OH) 2D3] can reduce the number (percentage) of Th17 cells and IL-17A levels in CD4+ Tcells culture of SLE patients with hipovitamin D.

Keywords: vitamin D, SLE, Th17, IL-17A



Poster Session: Session 1: Infection and autoimmunity

P1-047 HERPES ZOSTER INFECTION AMONG FILIPINOS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AT A SINGLE TERTIARY CARE CENTER
L.D. Zamora1, S.N. Leynes1, S.V. Navarra1


1Medicine Section of Rheumatology, University of Santo Tomas Hospital, Manila, Philippines

BACKGROUND AND OBJECTIVE: Herpes-zoster (HZ) has higher occurrence in systemic lupus erythematosus (SLE) compared to the general population. We aimed to identify clinical factors associated with HZ infections among Filipino SLE patients.

METHODS: We reviewed the medical records ofSLE patients seen at the University of Santo Tomas (UST) Hospital from 2008-2012 who were diagnosed with HZ, and described the following: site and dermatomal distribution of HZ, SLE disease characteristics, immunosuppressive use, response to anti-viral therapy and HZ recurrences.

RESULTS: The medical records of 320 SLE patients were reviewed for the occurrence of HZ. Of these, 52 (16.3%) developed HZ, with 4 patients having more than one episode of HZ. There were 48 (92%) females, the mean age was 34.7 years (range 10-65), and mean SLE disease duration at HZ infection was 50.4 months (range 2-204). The HZ lesions were all localized involving up to 3 dermatomes; none had disseminated disease. All cases were responsive to antiviral therapy. Average prednisone dose was 17.3 mg/day (range 0-60), with 80 % of patients also on hydroxychloroquine within the month preceding HZ infection. Recent use of cyclophosphamide or methylprednisolone pulse therapy was recorded in 16(31%) and 5(9.6%) patients, respectively, four patients each were receiving either azathioprine or mycophenolate mofetil.

CONCLUSION: HZ occurrence in this SLE cohort was 16.3%. Although 31% were on immunosuppressive medications, HZ outcomes were generally favourable.

FUNDING: Lupus-Inspired Advocacy (LUISA) Project of Rheumatology Educational Trust Fund Inc. (RETFI)
P1-048 PROSTATIC ABSCESS AS A PRESENTING FEATURE OF PARADOXICAL TB-IRIS
C.H. Mak1, B. Achappa1, A. Shenoy1


1Medicine, Kasturba Medical College Mangalore (Manipal University), MANGALORE DAKSHINA KANNADA DI, India

Paradoxical tuberculosis * immune reconstitution syndrome (pTB-IRIS) is a well recognized cause of clinical deterioration in HIV tuberculosis (HIV-TB) co-infected individuals following initiation of antiretroviral therapy (ART). pTB-IRIS is often reported as fever, lymphadenopathy & worsening of tuberculosis (TB) at a pre-existing site of infection.

A 39 year old male, known case of retroviral disease was diagnosed with toxoplasmosis and TB meningitis. He was started on antitubercular therapy (ATT) and steroids. Two weeks later, patient improved symptomatically and so ART was initiated. He came back with complaints of fever with chills. Patient was adherent to treatment. His CD4 count was 93 cells/mm3. Clinical examination revealed bilateral cervical lymphadenopathy. Investigations were sent to evaluate the cause of fever but all were negative. Ultrasonography of abdomen & pelvis showed a heterogenous hypoechoic lesion in the prostate with bulky right seminal vesicle, suggestive of an abscess. A transrectal ultrasound-guided aspiration of the prostate was carried out, which revealed acid fast bacilli. A complete drainage of the tuberculous prostatic abscess was performed and patient was treated with steroids whilst continuing ART and ATT. The patient improved symptomatically.

Although there was a strong clinical suspicion of pTB- IRIS, this case initially eluded the diagnosis and came across as pyrexia of unknown origin because the site of worsening of TB if any, was not easily recognizable. Patient did not report any complaints that could have suggest prostate involvement. This is probably the first reported case of pTB-IRIS reported in literature which manifested as a prostatic abscess.


P1-049 Challenges in the management of concomitant TB arthritis and AVN in a patient with adverse drug reaction to anti-Koch's medication-a case report
K. Tee1, A.D. Magbitang1, M.L. Tee1


1Section of rheumatology, Philippine General Hospital, Manila, Philippines

BACKGROUND: Non-traumatic avascular necrosis(AVN) of the bone commonly presents as monoarthritis. While corticosteroid still remains as one of the leading cause, several other factors have been associated with its development. This includes systemic lupus erythematosus(SLE). A large proportion of patients with AVN benefits from surgical procedures like core decompression. The presence of infection complicates its management.
A review of literatures showed only one case report of monoarticular tuberculous osteonecrosis diagnosed by aspiration cytology.
Since tuberculosis and osteonecrosis are destructive but curable disease, early diagnosis and treatment is essential.
OBJECTIVE: To present a case of osteonecrosis of the hip and knee complicated by tuberculous arthritis of the knee in a patient with SLE.
CASE: A 27 year old female who was diagnosed with lupus nephritis underwent 3 days methylprednisolone pulse therapy. Lupus nephritis improved and SLE activity is clinically inactive for 2 years.
She developed insidious onset of monoarthritis of the left knee lasting for 6 months, with subsequent right hip pain of 1 week duration. She underwent arthrocenthesis of the left knee. Synovial fluid PCR was consistent with tuberculosis. MRI of the left knee showed osteonecrosis and arthtritis. Radiograph of the right hip showed osteonecrosis. The patient was given anti-Koch's regimen and iloprost infusion with significant clinical improvement.
CONCLUSION: This is the first reported case of a lupus patient with concomitant polyarticular osteonecrosis complicated by monoarticular tuberculous arthritis. Medical treatment is effective for symptomatic management, but a multidisciplinary approach is suggested for optimal outcome.
P1-050 HEPATITIS B-ASSOCIATED POLYARTERITIS NODOSA PRESENTING AS MONONEURITIS MULTIPLEX: A CASE SERIES
M. Lazo1, J.P. Consignado1, S.T.V. Navarra1


1Section of Rheumatology, St. Luke's Medical Center, Quezon City, Philippines


Background:
Polyarteritis nodosa (PAN) is anANCA-negative systemic necrotizing vasculitis that typically affects medium-sized muscular arteries, withoccasional involvement of small muscular arteries. Infectious etiologies suchas Hepatitis B and C viruses and HIV are important in the pathogenesis of some ofthese cases. Hepatitis B-associated PAN (HBV-PAN) has the same clinicalfeatures as non-HBV-associated PAN and typically occurs within four months after the onset of HBV infection.
Cases: We presenttwo cases of HBV-PAN seen over a 6-year period in our institution. The firstcase was a 38 year-old male who presented with bilateral foot drop andhyperesthesia, weight loss, anorexia and fever, with EMG-NCV finding of severedistal, asymmetrical, neuronal axonal loss type of sensorimotor polyneuropathy.The second case is a 43 year-old male with severe paresthesia and progressiveweakness of the distal upper and lower extremities. EMG-NCV showed severe,diffuse, acute distal asymmetric sensorimotor axonal polyneuropathyaffecting the lower more thanthe upper extremities. Both patients had chronic active Hepatitis B infectionby serologic testing. Sural nerve biopsy was done in the 2 patients, results ofwhich were consistent with Polyarteritis Nodosa. Short-term steroid therapy,anti-viral agents and serial plasma exchange provided improved motor strengthand eventually led to good outcome in these patients.
Conclusion: HBV-PAN is an important consideration in patients presenting with vasculitic neuropathy, especially in countries where prevalence of Hepatitis B infection is high. Corticosteroids, in adjunct with plasma exchange and anti-viral therapy, are currently the cornerstone of treatment of HBV-PAN.
P1-051 HIGHER RESPONSE TO FEC PEPTIDE POOL STIMULATION IN RA PATIENTS UNDERGOING GOLIMUMAB THERAPY
A. Khanniche1, P.H.D. Jiang1


1School of medecine, Shanghai JiaoTong University, Shanghai, China

In order to investigate the susceptibility of RA patients to infections, we studied the functionality of virus specific memory T cell upon stimulation with FLU-EBV-CMV peptide pools. RA patients included in this part are under TNF-a inhibitor therapy (Golimumab) as we expect they may have more impaired memory T cells than patients without anti-TNF- a therapy.



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