Genetic markers in rheumatoid arthritis relationship to toxicity from D-penicillamine.
In a 3-centre study involving 144 patients with rheumatoid arthritis (RA), a relationship between side effects from D-penicillamine and HLA antigens, allotypic markers of the IgG heavy chain (Gm) and allotypes of complement components Bf, C4A and C4B was sought. There was a significant association between proteinuria induced by D-penicillamine and the antigens DR3 and B8. However, the presence of DR2 seemed to protect against the development of proteinuria. Thrombocytopenia from D-penicillamine was significantly associated with HLA-A1 and DR4; 15 of 23 patients who possessed both antigens developed thrombocytopenia (p less than 0.001 uncorrected, approximate relative risk (RR) = 5.5). A null complement allele located at the C4B locus (C4BQO) was also associated with thrombocytopenia from D-penicillamine (p less than 0.005, RR = 17.3). Our study confirms the findings from other series which indicate that there is a genetic predisposition for the development of proteinuria from D-penicillamine in RA and suggests that this may also be the case in D-penicillamine induced thrombocytopenia.
Stockman
A
A
Zilko
P J
PJ
Major
G A
GA
Tait
B D
BD
Property
D N
DN
Mathews
J D
JD
Hannah
M C
MC
McCluskey
J
J
Muirden
K D
KD
D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D004198:Disease Susceptibility; D005819:Genetic Markers; D006680:HLA Antigens / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000276:immunology; D009157:Myasthenia Gravis / Q000139:chemically induced*; D010396:Penicillamine / Q000009:adverse effects* / Q000627:therapeutic use; D011507:Proteinuria / Q000139:chemically induced*; D013921:Thrombocytopenia / Q000139:chemically induced*
D005819:Genetic Markers; D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II; D007126:Immunoglobulin Allotypes; D010396:Penicillamine