Anti-programmed cell death protein 1 (anti-PD1) immunotherapy induced autoimmune polyendocrine syndrome type II (APS-2): a case report and review of the literature

Table 1 Summary of Case Reports of anti-PD1/PD-L1 induced APS-2 (at least two components)

Author (year published)	Therapy	Age (years)	Country	Disease	Timing^a (weeks)	Conditions	auto-Ab found	HLA type	Response
Hakami [7] (2019)	pembrolizumab	52	Ireland	melanoma	21	hypothyroidism T1DM		NR	NR
Lanzolla [8] (2019)	atezolizumab	60	Italy	NSCLC	6	T1DM hypoadrenalism	anti-21-OH	DRB104 DQB103	PD
Sakurai [9] (2018)	nivolumab	68	Japan	RCC	14	hypothyroidism^b T1DM	anti-TPO Anti-Tg	DRB109:01 DQB103:03	NR
Gauci [10] (2017)	nivolumab	73	France	melanoma	6	hyperthyroidism^b T1DM	anti-GAD anti-IA2 anti-ZnT8	NR	PR
Paepegaey [11] (2017)	pembrolizumab	55	France	melanoma	12	hypothyroidism hypoadrenalism	anti-21-OH	NR	NR
Li [12] (2017)	nivolumab	63	USA	NSCLC	4	T1DM hypothyroidism	anti-GAD anti-TPO	NR	PD
Alhusseini [13] (2017)	pembrolizumab + ipilimumab	65	USA	NSCLC	3	T1DM hyperthyroidism	anti-GAD anti-IA anti-insulin anti-TPO	NR	PR
Lowe [14] (2016)	nivolumab + ipilimumab	54	USA	melanoma	2	hyperthyroidism T1DM	anti-GAD	DQB1*0602	CR
Kong [15] (2016)	pembrolizumab	68	Korea	NSCLC	21	T1DM hyperthyroidism	Nil	DRB109:01 DQB103:03	PR
Hansen [16] (2016)	pembrolizumab	58	USA	melanoma	NR	hypothyroidism T1DM	anti-GAD	NR	PR
Mellati [17] (2015)	NR	66		SCC jaw	7	T1DM hypothyroidism	anti-TPO anti-GAD	DR3-DQ2 DR4-DQ8	NR
Hughes [18] (2015)	nivolumab + ipilimumab	55	USA	melanoma	20	hypothyroidism^b T1DM		A2.1 DR4	NR
Hughes (2015)	pembrolizumab	64	USA	melanoma	< 4	hypothyroidism^b T1DM		DR4	NR

Abbreviations: auto-Ab auto-antibody, HLA Human leukocyte antigen, T1DM Type 1 diabetes mellitus, NR Not reported, PD Progressive disease, 21-OH 21-hydroxylase, anti-TPO Anti-thyroid peroxidase, anti-Tg anti-thyroglobulin, anti-GAD anti-glutamic acid decarboxylase, anti-IA2 anti-islet antibody 2, anti-ZnT8 anti-zinc transporter 8, PR partial response, CR complete response
^atiming denotes weeks after start of anti-PD1 therapy to onset of APS-2
^bauto-immune condition preceded treatment with anti-PD1 axis therapy