Division of Rheumatology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
Division of Rheumatology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
RMD Open. 2022 Sep;8(2). doi: 10.1136/rmdopen-2022-002511.
Patients with inflammatory arthritis (IA) associated with immune checkpoint inhibitor (ICI) treatment for cancer are typically seronegative for anti-cyclic citrullinated peptide (CCP) antibodies and rheumatoid factor, but little is known about the presence of other autoantibodies in this patient population. We investigated the prevalence and characteristics of anti-RA33 antibodies in patients with ICI-induced IA.
Anti-RA33 ELISAs were performed on sera from four groups of patients: 79 with ICI-induced IA, 52 with rheumatoid arthritis (RA), 35 treated with ICIs without IA during follow-up and 50 healthy controls. Anti-RA33 positivity and level, clinical and demographic data were compared across groups.
Anti-RA33 antibodies were found in 9/79 (11.4%) patients with ICI-induced IA but in 0/35 patients treated with ICIs who did not develop IA (0%; p=0.04). Of the patients positive for anti-RA33, two had sera available from before ICI treatment; anti-RA33 antibodies were present in both pre-ICI treatments. In patients with RA, 7.7% were positive for anti-RA33 antibodies as were 2% of healthy controls. In ICI-induced IA, anti-RA33 antibodies were associated with anti-CCP antibodies (p=0.001). We found no statistically significant differences in other clinical characteristics in those with and without anti-RA33 antibodies.
Anti-RA33 antibodies are present in a subset of patients with ICI-induced IA, absent in other ICI-treated patients and may be a biomarker for developing IA. Additional studies evaluating serial samples before and after ICI treatment will further establish the temporal relationship of these antibodies to IA development.
接受免疫检查点抑制剂（ICI）治疗癌症相关炎症性关节炎（IA）的患者通常抗环瓜氨酸肽（CCP）抗体和类风湿因子阴性，但对于此类患者人群中其他自身抗体的存在知之甚少。我们研究了 ICI 诱导的 IA 患者中抗 RA33 抗体的患病率和特征。
对四组患者的血清进行抗 RA33 ELISA 检测：79 例 ICI 诱导的 IA 患者、52 例类风湿关节炎（RA）患者、35 例随访期间未发生 IA 的接受 ICI 治疗的患者和 50 例健康对照者。比较各组之间抗 RA33 阳性率和水平、临床和人口统计学数据。
在 79 例 ICI 诱导的 IA 患者中发现 9 例（11.4%）存在抗 RA33 抗体，但在未发生 IA 的 35 例接受 ICI 治疗的患者中无一例（0%；p=0.04）存在抗 RA33 抗体。在抗 RA33 阳性的患者中，有 2 例患者在接受 ICI 治疗前有血清样本可用，在这 2 例患者的 ICI 治疗前的血清样本中均存在抗 RA33 抗体。在 RA 患者中，有 7.7%的患者抗 RA33 抗体阳性，健康对照者中也有 2%的患者抗 RA33 抗体阳性。在 ICI 诱导的 IA 中，抗 RA33 抗体与抗 CCP 抗体相关（p=0.001）。我们发现，在有无抗 RA33 抗体的患者之间，其他临床特征无统计学显著差异。
抗 RA33 抗体存在于接受 ICI 治疗的部分患者中，在其他接受 ICI 治疗的患者中不存在，可能是发生 IA 的生物标志物。进一步评估 ICI 治疗前后的系列样本的研究将进一步确定这些抗体与 IA 发生之间的时间关系。
