Table 3.

Overview of autoimmune diseases hallmarked by high levels of IgG4 autoantibodies, but with poorly defined roles for IgG4 in the disease.

Antigen	Disease	Symptoms	Prevalence	HLA association	Target organ	Main immunogenic region	Passive transfer confirmation in experimental animals	Disease mechanism	VDJ gene usage	Reference
ACPA	Rheumatoid arthritis	Stiff hands and feet joints due to chronic inflammation	~ 60% of all rheumatoid arthristis patients	DRB1*01:01,01:02 DBR1*04:01,*04:04,*04:05,*04:08 DRB1*09:01 DRB1*10:01	Joints	Different citrullinated proteins carry the epitope: fibrin, fibrinogen, enolase, collagen, vimentin, and EBNA	Yes, partially. Passive transfer can exacerbate disease	Mixed effects of both IgG1 and IgG4 autoantibodies. Inflammation plays a key role.	Varying dependent on antigen	71, 88
BP180 (type XVII collagen)	Bullous pemphigoid	Acantholysis (skin blistering)	10 per million	HLA-DQB1*0301 HLA-DRB1*04, HLA-DRB1*1101, HLA-DQB1*0302	Skin hemidesmosomes	Non-collagenous 16A domain	Yes	Mixed effects of both IgG1 and IgG4 autoantibodies. Complement is likely involved.	VH4	12, 80
BP230 (dystonin-e)	Bullous pemphigoid	Acantholysis (skin blistering)	10 per million	HLA-DQB1*0301	Skin hemidesmosomes	Broad response, epitopes throughout the antigen, but most against collagen B and C subdomains	N/A	Mixed effects of both IgG1 and IgG4 autoantibodies. Complement is likely involved	N/A	12, 86
Collagen IV	Goodpasture disease	Alveolar hemorrhage and glomerulonephritis	1 per million	HLA-DRB1*1501	Kidney	α3(IV)NCI-domain	Yes	Unclear if involved in pathogenesis, mostly IgG1–3	V1-8 V3-48 V3-21 V-3-23 V1-69 Derived from humanized model	78
DPPX	Encephalitis	Memory and cognitive dysfunction, seizures, hyperekplexia, tremor, diarrhea	39 patients described	N/A	CNS, hippocampus	N/A	N/A	Decreased expression of DPPX and Kv4.2. Increased excitability and action potential frequency	N/A	13