Table 1:

HLA class II allele association with hypersensitivity to IL-1 and IL-6 inhibitors¹

HLA allele	Ancestry	Cases	Controls
		Still’s-DRESS2	Still’s controls	INCHARGE sJIA	P value3	OR (95% CI)
DRB1*15:01	European vs European	13/14 (93%)		130/550 (24%)	2.7×10−7	40.8 (5.3, 316)
	self-ID White vs European	30/36 (83%)		130/550 (24%)	7.5×10−13	15.5 (6.3, 38.1)
DRB1*15:014	self-ID White	30/36 (83%)	0/19 (0%)		6.3×10−10	Inf (16.05-Inf)
	self-ID non-White	16/28 (57%)	0/11 (0%)
DRB1*15:XX4		21/28 (75%)	2/11 (18%)
Kawasaki disease		KD-sAR	Drug-tolerant KD
DRB1*15:01	All	2/4 (50%)	0/15 (0%)
DRB1*15:XX	All	3/4 (75%)	2/15 (13%)5
Still’s + Kawasaki disease		Still’s-DRESS + KD-sAR	Drug-tolerant Still’s + KD
DRB1*15:01	All	48/68 (71%)	0/45 (0%)
DRB1*15:XX	All	54/68 (79%)	4/45 (9%)
DQB1*06:02	All	47/65 (72%)	3/45 (7%)

DRESS, Drug reaction with eosinophilia and systemic symptoms classified per RegiSCAR²⁰; INCHARGE, International Childhood Arthritis Genetics Consortium¹⁸; OR (95% CI), Odds ratio and 95% confidence interval; European: Still’s-DRESS cases were ancestry-matched by PCA to the INCHARGE Still’s (sJIA) cohort (figure S1); self-ID, self-identified; White, similar to European descent; Inf, infinite; KD, Kawasaki disease; HLA-DRB1*15:XX, all HLA-DRB1*15 alleles

¹In analyses omitting AOSD patients, similar results were obtained (table S5).

²Includes one case with suspected anakinra reaction (see methods).

³P value, top two rows are by logistic regression from multi-allelic comparison to the INCHARGE cohort; only DRB1*15:01 result is shown (extended results on tables S4a–c). Bonferroni corrected P<2.0×10⁻⁴. P-value in third row is by Fisher’s exact test, comparing Still’s-DRESS to Still’s controls for DRB1*15:01.

⁴Each HLA-DR allele group observed in self-identified White Still’s DRESS subjects initially was interrogated for association; only HLA-DRB1*15 alleles showed significant association (table S6).

⁵HLA-DRB1*15:02 in two individuals, treated briefly (12d and 28d) with anakinra.