Dr Antigens and Gold Toxicity in white rheumatoid arthritis patients

Abstract

An increase in the frequency of DR3 in rheumatoid arthritis (RA) patients exhibiting toxic reactions to chrysotherapy has been reported in several studies of white patients. This study was designed to compare DR antigen frequencies in local white RA patients undergoing chrysotherapy with their response to treatment. The results from our sample of RA patients (n = 148) confirm the fact that there is increased frequency of DR3 in patients who develop toxic reactions to gold therapy, as reported in other studies of white patients. The DR3 increase was attributable to those gold‐treated patients who developed proteinuria, and was not observed in patients who developed skin toxicity. Interestingly, the associations were not as strong as those found in other reports. Only 21.1% of the patients with DR3 manifested toxic reactions overall, with only one‐third of the patients with proteinuria being DR3 positive. There was also an association of toxicity, albeit not significant, with a decreased frequency of DR2, which is consistent with the suggestion that this phenotype may protect against adverse reactions to gold treatment. These results suggest that while DR3 is significantly associated with adverse response to gold treatment, the relationship is not as strong as that previously reported. Explanation of these differences remains to be elucidated.

Clinical pharmacology of gold

“…HLA-DR2 may be associated with mouth ulcers (Panayi et al, 1979) but this association between HLA-DR2 and toxicity in general has been disputed. Several reports suggest that HLA-DR2 and also HLA-DR7 may protect patients from the development of toxicity, and like HLA-DR4, the HLA-DR2 group may be a disease modifier (Repice et al, 1979;Barger et al, 1984). Panayi and his colleagues later reported that 79 % of patients with HLA-DR3/B8 developed proteinuria while being treated with gold (14 out of 15) or D-penicillamine (9 out of l3) (Wooley et al, 1980).…”

Metals and Kidney Autoimmunity

“…Proteinuria was detected in 6-17% and a nephrotic syndrome in 2.6-5.3% of RA patients treated with gold salts (86). The relative risk of proteinuria during gold treatment of RA was increased 32 times in patients who were HLA-DR3 positive (122)(123)(124)(125). A survey of 122 RA patients who underwent kidney biopsy after the development of proteinuria showed that 41% of these subjects presented with a nephrotic syndrome.…”

Nephrotoxicity of gold salts, D-penicillamine, and allopurinol

“…Proteinuria including nephrotic syndrome is the commonest manifestation of gold-induced nephropathy, occurring with a frequency of 2 to 10% in patients with chrysotherapy [10,[22][23][24]. The risk of proteinuria is increased at higher doses [26] and in the patients with HLA DR3 [27][28][29][30]. In one-third to half of the patients, the proteinuria is accompanied by microscopic hematuria [31,32].…”

“…Furthermore, all 13 episodes of proteinuria exceeding 2 g/day occurred in patients with DRw3. Several investigators confirmed the association between gold-induced proteinuria and DR3 [27][28][29][30] and B8 [30], but others could not confirm it [72]. On the other hand, the patients carrying DR3 tend to exhibit a better therapeutic response to sodium aurothiomalate than patients with DR4 [28].…”

“…On the other hand, the patients carrying DR3 tend to exhibit a better therapeutic response to sodium aurothiomalate than patients with DR4 [28]. DR4 and/or DR2 positive patients may have some degree of protection against gold toxicity [28,29]. Given the uncertainty about HLAtypes and toxic reactions, together with the suggestion that patients with DR3 respond better than those bearing the more common DR4, and taking into account the cost involved, any suggestion of using HLA typing as a guide to therapy seems premature [73].…”