Biomarkers associated with immune-related adverse events induced by immune checkpoint inhibitors

Table 3 Autoantibodies and metabolic abnormalities biomarkers of immune-related adverse events

Biomarker	ICI type	No. of patients	Study cohort	irAEs type	Judgment	Ref.
Thyroglobulin	CTLA-4, PD-1	26	13/26 (50%) irAEs	Thyroid dysfunction	The titers of TgAb and TPO in the irAE group were significantly higher after ICI treatment	[43]
TgAb, TPOAb	CTLA-4, PD-1	26	13/26 (50%) irAEs	Thyroid dysfunction	Serum Tg level in irAE group increased significantly before/after treatment	[43]
Thyroid-stimulating hormone	CTLA-4, PD-1	96	36/96 (37.5%) irAEs	Thyroid gland irAEs	High thyroid-stimulating hormone levels at baseline are associated with a higher risk of hypothyroidism	[65]
Anti-pituitary antibodies	CTLA-4, PD-1	62	17/62 (27%) ICI- ICI-induced isolated adrenocorticotropic hormone deficiency, 5/62 (8%) ICI-induced hypophysitis	Pituitary gland irAEs	Patients with ICI-induced isolated adrenocorticotropic hormone deficiency showed positive anti-pituitary antibodies at baseline and after treatment, and patients with ICI-induced hypophysitis showed positive anti-pituitary antibodies after treatment and before onset, and anti-pituitary antibodies can be used as biological predictors	[66]
Anti-GNAL and anti-ITM2B autoantibody		9 + 20	Study cohort: 3 hypophysitis, 6 non-hypophysitis; Confirmed cohort: 5 pituitaritis, 15 non-pituitaritis	Pituitary gland irAEs	Anti-GNAL and anti-ITM2B were associated with irAE hypophysitis	[67]
Anti-CD74 autoantibody		8 + 32	Study cohort: 2 pneumonia, 6 non-pneumonia; Confirmed cohort: 10 pneumonia, 22 non-pneumonia	Lung irAEs	Anti-CD74 autoantibody is associated with irAE pneumonia	[67]
Antinuclear antibody	PD-1	83	6/18 (33.3%) irAEs in antinuclear antibody positive group. 21/65 (32.3%) irAEs in antinuclear antibody negative group		The incidence of irAEs increased with antinuclear antibody titer	[68]
Urine retinol binding protein/urine creatinine	CTLA-4, PD-1, PD-L1	50	37/50 (74%) irAEs	Kidney irAEs	During the occurrence of ICI-induced acute kidney injury, the urine retinol binding protein/urine creatinine value of patients was significantly higher	[69]
Guanylate binding protein 5, Guanylate binding protein 6	CTLA-4, PD-1	19	All 19 patients were suspected of cardiac irAEs	Heart irAEs	Guanylate binding proteins 5 and 6 were significantly upregulated in ICI-induced myocarditis compared with dilated cardiomyopathy and virus-induced myocarditis	[70]

irAEs: Immune-related adverse events; ICI: Immune checkpoint inhibitors; TgAb: Anti-thyroglobulin antibodies; TPOAb: Thyroid peroxidase antibodies.