PMID- 14522089
OWN - NLM
STAT- MEDLINE
DCOM- 20040527
LR  - 20190906
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 64
IP  - 10
DP  - 2003 Oct
TI  - Functional categorization of HLA-DRB1 alleles in rheumatoid arthritis: the 
      protective effect.
PG  - 930-5
AB  - Because of past recombination event, human leukocyte antigen (HLA) alleles that 
      are not closely related in overall sequence may come to resemble each other in 
      areas coding for peptide binding regions (PBR) of HLA molecules. Peptide binding 
      is likely to be important for the role of HLA molecules in autoimmune disease. As 
      a result, it has been suggested that a strategy of searching for HLA disease 
      associations that groups alleles in functional categories based on PBR motifs may 
      be more successful than conventional strategies based on studying different 
      alleles. Using such functional categorization, we examined the possibility of 
      discriminating subcategories of HLA-DRB1 alleles associated with rheumatoid 
      arthritis (RA) in a Southern French population. HLA-DRB1 genotyping was performed 
      by polymerase chain reaction with sequence-specific oligonucleotide hybridization 
      or sequence-specific primers. HLA-DRB1 alleles were classified according to a 
      functional categorization that defined seven similar subregion structures or 
      restrictive supertype patterns (RSPs) within pocket 4 of HLA-DR peptide binding 
      groove as the molecular basis for grouping these alleles. HLA-DRB1* RSPs "A," 
      "De," "Q," "Dr," "E," " R," and "a" association with susceptibility or resistance 
      to disease was then studied in 200 RA patients versus 200 controls. DRB1* RSP "A" 
      containing the shared epitope alleles (DRB1*0101, *0102, *0401, *0404, *0405, 
      *0408, *1001, *1402; odds ratio [OR] = 4.35; pc < 0.001) had a predisposing 
      effect, with double-dose effect as expected, OR 6.68 (pc < 0.001). Among the six 
      remaining RSPs, two had significantly protective effect: DRB1* RSP "De" 
      (DRB1*0103, *0402, *1102, *1103, *1301, *1302, *1304; OR = 0.33; p(c) < 0.001), 
      and DRB1* RSP "Q" (DRB1*0701; OR = 0.40; pc < 0.001). One had non-significantly 
      protective effect: DRB1* RSP "Dr" (DRB1*08, *1101, *1104, *1106, *12, *1303, *16; 
      OR = 0.68; p < 0.05, pc = not significant [NS]). Three had neutral effect: 
      HLA-DRB1* RSPs "E" (DRB1*0403, *0407, *0901, *1401; OR = 0.71; p = NS), " R" 
      (DRB1*0301, *0302; OR = 0.76; p = NS), and "a" (DRB1*1501, *1502; OR = 0.94; p = 
      NS). The functional categorization allowed us to discriminate among the HLA-DRB1 
      alleles those that confer a predisposing effect, a neutral effect, and a 
      protective effect in RA.
FAU - Gibert, Morgane
AU  - Gibert M
AD  - Faculte de Medecine, UMR 6578 Adaptabilite Humaine, Anthropologie Biologique et 
      Culturelle, INSERM EMI 9940, Universite de la Mediterranee, Marseilles, France. 
      morganegibert@netcourrier.com
FAU - Balandraud, Nathalie
AU  - Balandraud N
FAU - Touinssi, Mhammed
AU  - Touinssi M
FAU - Mercier, Pierre
AU  - Mercier P
FAU - Roudier, Jean
AU  - Roudier J
FAU - Reviron, Denis
AU  - Reviron D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*03:01 antigen)
SB  - IM
MH  - Alleles
MH  - Arthritis, Rheumatoid/*genetics/immunology
MH  - Gene Frequency
MH  - *Genetic Predisposition to Disease
MH  - HLA-DR Antigens/*genetics/immunology
MH  - HLA-DRB1 Chains
MH  - Humans
EDAT- 2003/10/03 05:00
MHDA- 2004/05/28 05:00
CRDT- 2003/10/03 05:00
PHST- 2003/10/03 05:00 [pubmed]
PHST- 2004/05/28 05:00 [medline]
PHST- 2003/10/03 05:00 [entrez]
AID - S0198885903001861 [pii]
AID - 10.1016/s0198-8859(03)00186-1 [doi]
PST - ppublish
SO  - Hum Immunol. 2003 Oct;64(10):930-5. doi: 10.1016/s0198-8859(03)00186-1.