Table 2.
Summary of IgG4-AID vs. IgG4-RLD.
| Disease aspects | IgG4 autoimmune diseases (IgG4-AID) | IgG4-related diseases (IgG4-RLD) | References |
|---|---|---|---|
| Prevalence†, (per 10,000) | <0.0001 – 5 | 0.028 – 0.108 (Japan) | (3, 8, 9, 31) |
| Gender predisposition†, | MuSK MG, pemphigus, thrombotic thrombocytopenic purpura: female predominance LGI1, Caspr2 encephalitis, CIDP (NF155, CNTN1): male predominance |
Male predominance | (32–36) |
| Affected organs | Currently known: nervous system, kidneys, blood, skin and mucosa | All organs/multiorgan, often in salivary glands, lymph nodes and pancreas | (3, 37) |
| Fibrosis | No | Yes‡ | (37) |
| Tissue infiltrates of IgG4+ lymphocytes | No | Yes‡ | (37) |
| Organ enlargement, tumor-like mass formation in affected organ | No | Yes, often in lacrimal glands, orbits, major salivary glands, pancreas, bile ducts, retroperitoneum, lungs, kidneys, aorta, pachymeninges and thyroid gland | (37) |
| Suspected HLA risk loci | HLA-DRB1*14, HLA-DQB1*05, HLA-DRB1*14-DQB1*05, HLA-DRB1*15, HLA-DRB1*04, DRB1*03 protective |
HLA-DRB1*04:05, HLA-DQB1*04:01, HLA-A, HLA-C, HLA I, HLA-DQB1*03:02, HLA-B*07, HLA-B*08, HLA-DRB1*15 |
(38, 39) |
| IgG4 concentrations | Normal | Elevated (≥1.35g/L in 70% of patients)‡ | (14) |
| Autoantigen-specific IgG4 | In 100% of cases‡ | In a subset of patients | (3, 40) |
| Location of known IgG4 autoantigen | Extracellular | Intracellular and extracellular | (3, 40) |
| Role of IgG4 | Directly pathogenic‡ | Unclear | (3, 40) |
| Pathogenic mechanism of IgG4 | IgG4 blocks protein-protein interactions | Unknown | (3, 40) |
| Treatment response | Moderate success of corticosteroid treatment. B cell depletion beneficial especially in treatment resistant patients | Moderate success of corticosteroid treatment. B cell depletion beneficial especially in treatment resistant patients | (3, 41, 42) |
†Few epidemiological data available, the values shall be considered as estimates. ‡characteristics are considered as pathognomonic. Caspr2, contactin-associated protein-like 2; CIDP, chronic inflammatory demyelinating polyneuropathy; CNTN1, contactin 1; HLA, human leucocyte antigen; IgG4, immunoglobulin type G subclass 4; LGI1, leucine-rich glioma inactivated protein- 1; MG, myasthenia gravis; MuSK, muscle-specific kinase; NF155, neurofascin 155.