ICI-Induced Inflammatory Arthritis and Shared Epitope Alleles

Rachel Tate, DO

Oct 21, 2018 3:46 pm

Immune checkpoint inhibitors (ICI) have changed the hematology/oncology world. However, their AEs from a rheumatologic standpoint are still being evaluated and at this time, genetic risk factors for inflammatory arthritis due to ICI are not well understood. Dr. Cappelli et al evaluated a possible connection with HLA typing at their institution.

There were 27 patients with ICI-induced IA (targeting CTLA-4, PD-1, and/or PD-L1 for Melanoma (most common), non-small cell lung cancer, renal cell carcinoma, basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, mycosis fungoides, colon, endometrial, esophageal, and breast cancers) and 726 controls who were prospective bone marrow donors who underwent high resolution HLA typing.

Genotyping at the shared epitope (SE) locus (HLA-DRB1) was also performed on 220 rheumatoid arthritis (RA) cases.

Fisher’s exact test was used to compare allele-positivity rates and the frequency of having at least one SE allele was compared between RA and population controls and ICI-induced IA patients.

One patient was AA and no correlate was found, but of the 26 European descent patients, 16 (61.5%) had at least one SE allele which differed significantly from the European descent bone marrow donor controls where 299 (41.2%) had at least one SE allele (OR=2.3, p=0.04).

The DRB1*04:05 allele was statistically different between groups, yet there were higher rates of HLA A*03:01, B*52:01, and C*12:02 in patients with ICI-induced IA. Those patients were more likely to have a negative CCP and RF but the population did not differ significantly from RA patients of European in terms of frequency of having at least one SE allele.

Cappelli LC, Dorak MT, Bingham III CO, Shah AA. Association of HLA-DRB1 Shared Epitope Alleles with Immune Checkpoint Inhibitor-Induced Inflammatory Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/association-of-hla-drb1-shared-epitope.... Accessed October 15, 2018.