IgG4 autoimmune diseases

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IgG4 autoimmune diseases are a group of autoimmune diseases caused by antigen-specific autoantibodies of the immunoglobulin G subclass IgG4. The diseases include MuSK-positive myasthenia gravis , pemphigus vulgaris , pemphigus foliaceus , thrombotic-thrombocytopenic purpura or idiopathic membranous glomerulonephritis .

In contrast to the group of IgG4-related diseases, fibrosis, IgG4 plasma cell infiltrates and increased IgG4 serum levels are usually not observed.

Epidemiology

IgG4 autoimmune diseases are rare, with prevalence up to a maximum of 5 per 10,000 inhabitants.

illness antigen Prevalence per 10,000 population
MuSK Myasthenia gravis Muscle specific kinase / MuSK 0.02
Chronic inflammatory demyelinating polyneuropathy Contactin-1 / CNTN1 <0.014
Peripheral neuropathy , chronic inflammatory demyelinating polyneuropathy Neurofascin 155 / NF155 <0.014
Pemphigus foliaceus Desmoglein 1 / Dsg1 0.1-0.95
Pemphigus vulgaris Desmoglein 3 / Dsg3 1-5
Thrombotic thrombocytopenic purpura A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 / ADAMTS13 1-5
Various diseases of the peripheral and central nervous system, e.g. limbic encephalitis Contactin-associated protein-like 2 / CASPR2 unknown
Limbic encephalitis Leucine-rich, glioma inactivated 1 / LGI1 unknown
Primary membranous glomerulonephritis Phospholipase A 2 receptor / PLA2R 0.1
Primary membranous glomerulonephritis Thrombospondin Type 1 Domain Containing 7A / THSD7A 0.003
Chronic inflammatory demyelinating polyneuropathy Contactin-associated protein-like 1 / CASPR1 <0.014
Goodpasture Syndrome Type IV collagen 0.001-0.009
Autoimmune encephalopathy with parasomnia and obstructive sleep apnea / IgLON5 parasomnia IgLON Family Member 5 / IgLON5 <0.001
Limbic encephalitis with DPP6 antibodies Dipeptidyl-peptidase-like protein 6 / DPPX <0.001

Disease mechanism

IgG4 autoantibodies block important binding sites on proteins and prevent their normal function in the body. Here are protein-protein interactions blocked, which leads to the interruption of signal transduction pathways , loss of cell adhesion or blocking of enzymes , or receptors . For example, antibodies against the muscle-specific kinase (MuSK) block the interaction with the protein lipoprotein receptor-related protein 4 (Lrp4) and thus prevent the signal transduction for the aggregation of acetylcholine receptors (AChR) at the neuromuscular synapse . This leads to a reduced receptor density and impairment of the neuromuscular stimulus transmission , which leads to fatiguing muscle weakness .

diagnosis

A classification system exists to identify IgG4 autoimmune diseases. The pathogenicity of the IgG4 autoantibodies is determined here. To do this, three criteria must be met:

  1. The IgG4 autoantibodies must recognize a specific antigen that is present in the affected organ.
  2. A disease mechanism must be detectable in vitro.
  3. It must be possible to reproduce the disease in animal models by passive transfer of isolated IgG4 from patient serum.

Individual evidence

  1. ↑ MG Huijbers, LA Querol, EH Niks, JJ Plomp, SM van der Maarel, F. Graus, J. Dalmau, I. Illa and JJ Verschuuren, The expanding field of IgG4-mediated neurological autoimmune disorders, Eur J Neurol 22 (2015 ) 1151-61.
  2. ↑ I. Koneczny, A New Classification System for IgG4 autoantibodies, Frontiers in immunology 9 (2018) 97th
  3. ↑ Orpha.net
  4. ↑ I. Koneczny, A New Classification System for IgG4 autoantibodies, Frontiers in immunology 9 (2018) 97th