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DNA typing for HLA class II alleles in rheumatoid arthritis (RA) patients from North China
Abstracts
59
C-5.2 #105
DNA T Y P I N G FOR HLA CLASS II A L L E L E S IN R H E U M A T O I D A R T H R I T I S (RA) P A T I E N T S FROM N O R T H CHINA. y Sun, MA F e r n a n d e z - V i ~ a , Z Liu, L Kong, F Zhao and P Stastny. D e p a r t m e n t of Internal M e d i c i n e , U n i v e r s i t y of Texas S o u t h w e s t e r n M e d i c a l Center, Dallas, TX. In this study 85 p a t i e n t s w i t h r h e u m a t o i d a r t h r i t i s (RA) all RF+ and m a t c h e d c o n t r o l s from N o r t h China w e r e DNA typed for DRBI/3/5, DQAI, DQBI and DPBI alleles. H L A - D R 4 was s i g n i f i c a n t l y i n c r e a s e d in RA p a t i e n t s (47%) c o m p a r e d to m a t c h e d c o n t r o l s (25.3%, RR=2.5, P=O.O07). D R B I * 0 4 0 5 was the predominant DR s u b s e t (RR=5.1, P=0.0002). In addition, DRBI*I001 was increased in p a t i e n t s (RR=4.82, P=0.02). DQAI*0301, D Q B I * 0 4 0 1 and D Q B I * 0 5 0 1 w e r e a l s o i n c r e a s e d since they w e r e always a s s o c i a t e d w i t h D R B I * 0 4 0 5 and DRBI*I001. The c o m b i n a t i o n of DRBI*0101, 0401, 0404, 0405, 0408, i001, and 1402, a n a l y z e d on the basis of t h e i r s h a r e d e p i t o p e in the third HVR, a c c o u n t e d for 60% of the p a t i e n t s and the o v e r a l l RR was 2.6 (P=0.004). Our r e s u l t s indicate that D R B I * 0 4 0 5 and D R B I * I 0 0 1 are the s t r o n g e s t risk factors for RA in this population, but other DRBI a l l e l e s that have a s i m i l a r s e q u e n c e in the 3rd H V R may be also important. D R B I * 0 4 0 5 was p r e v i o u s l y found to be the m a i n risk factor in J a p a n e s e and in Israeli Jews and D R B I * I 0 0 1 was also found to be a s s o c i a t e d w i t h RA in Israeli Jews.
C-5.2 #106
T CELL RECEPTOR (TCR) VII NULL ALLELES IN JUVENILE RHEUMATOID ARTHRITIS (JRA). KS Barron. H Deulofeut, JD Reveille, MA Robinson. Laboratory of Immunogenetics, NIAID, NIH, Rockville, MD. and The University of Texas Health Science Center, Houston, TX. JRA is a heterogeneous disease with increasing evidence of MHC Class II associations. Because of its involvement in antigen recognition, the TCR repertoire may play a role in increased disease susceptibility. Three VI3 genes (VI36.1, 12.x, and 20) have been found to have allelic forms that are not likely to be expressed due to the presence of inframe stop codons or substitutions in highly conserved residues. To better define the relationship of the TCR to JRA, 43 pts with pauciarticular JRA (PaJRA) (28 onset <5 yrs; 31 ANA+), 50 pts with RFpolyarticular JRA (PoJRA), and 16 pts with RF+ polyarticular JRA (RF+JRA) were examined for the presence of these null alleles using single stranded conformational polymorphism and compared with 96 normal local controls. The presence of at least 1 null allele for each of these Vi3's was determined: Vii6.1 null a,llele vB12.x null allele VB20 null allele %.._~_+ ~ RR= %+ D-- RR= %+ ~ RR= Controls 49 42 54 PaJRA 72 .02 2.7 70 .02 3.1 53 onset >5 89 .004 8.3 80 .04 5.6 67 ANA+ 80 .005 4.2 76 .02 4.5 39 POJRA 58 67 .02 2.8 50 RF+JRA 25 29 0 .003 0.07 Thus, it appears that "holes" in the T cell repertoire may play a role in disease susceptibility to a number of JRA clinical subsets.
59
C-5.2 #105
DNA T Y P I N G FOR HLA CLASS II A L L E L E S IN R H E U M A T O I D A R T H R I T I S (RA) P A T I E N T S FROM N O R T H CHINA. y Sun, MA F e r n a n d e z - V i ~ a , Z Liu, L Kong, F Zhao and P Stastny. D e p a r t m e n t of Internal M e d i c i n e , U n i v e r s i t y of Texas S o u t h w e s t e r n M e d i c a l Center, Dallas, TX. In this study 85 p a t i e n t s w i t h r h e u m a t o i d a r t h r i t i s (RA) all RF+ and m a t c h e d c o n t r o l s from N o r t h China w e r e DNA typed for DRBI/3/5, DQAI, DQBI and DPBI alleles. H L A - D R 4 was s i g n i f i c a n t l y i n c r e a s e d in RA p a t i e n t s (47%) c o m p a r e d to m a t c h e d c o n t r o l s (25.3%, RR=2.5, P=O.O07). D R B I * 0 4 0 5 was the predominant DR s u b s e t (RR=5.1, P=0.0002). In addition, DRBI*I001 was increased in p a t i e n t s (RR=4.82, P=0.02). DQAI*0301, D Q B I * 0 4 0 1 and D Q B I * 0 5 0 1 w e r e a l s o i n c r e a s e d since they w e r e always a s s o c i a t e d w i t h D R B I * 0 4 0 5 and DRBI*I001. The c o m b i n a t i o n of DRBI*0101, 0401, 0404, 0405, 0408, i001, and 1402, a n a l y z e d on the basis of t h e i r s h a r e d e p i t o p e in the third HVR, a c c o u n t e d for 60% of the p a t i e n t s and the o v e r a l l RR was 2.6 (P=0.004). Our r e s u l t s indicate that D R B I * 0 4 0 5 and D R B I * I 0 0 1 are the s t r o n g e s t risk factors for RA in this population, but other DRBI a l l e l e s that have a s i m i l a r s e q u e n c e in the 3rd H V R may be also important. D R B I * 0 4 0 5 was p r e v i o u s l y found to be the m a i n risk factor in J a p a n e s e and in Israeli Jews and D R B I * I 0 0 1 was also found to be a s s o c i a t e d w i t h RA in Israeli Jews.
C-5.2 #106
T CELL RECEPTOR (TCR) VII NULL ALLELES IN JUVENILE RHEUMATOID ARTHRITIS (JRA). KS Barron. H Deulofeut, JD Reveille, MA Robinson. Laboratory of Immunogenetics, NIAID, NIH, Rockville, MD. and The University of Texas Health Science Center, Houston, TX. JRA is a heterogeneous disease with increasing evidence of MHC Class II associations. Because of its involvement in antigen recognition, the TCR repertoire may play a role in increased disease susceptibility. Three VI3 genes (VI36.1, 12.x, and 20) have been found to have allelic forms that are not likely to be expressed due to the presence of inframe stop codons or substitutions in highly conserved residues. To better define the relationship of the TCR to JRA, 43 pts with pauciarticular JRA (PaJRA) (28 onset <5 yrs; 31 ANA+), 50 pts with RFpolyarticular JRA (PoJRA), and 16 pts with RF+ polyarticular JRA (RF+JRA) were examined for the presence of these null alleles using single stranded conformational polymorphism and compared with 96 normal local controls. The presence of at least 1 null allele for each of these Vi3's was determined: Vii6.1 null a,llele vB12.x null allele VB20 null allele %.._~_+ ~ RR= %+ D-- RR= %+ ~ RR= Controls 49 42 54 PaJRA 72 .02 2.7 70 .02 3.1 53 onset >5 89 .004 8.3 80 .04 5.6 67 ANA+ 80 .005 4.2 76 .02 4.5 39 POJRA 58 67 .02 2.8 50 RF+JRA 25 29 0 .003 0.07 Thus, it appears that "holes" in the T cell repertoire may play a role in disease susceptibility to a number of JRA clinical subsets.