**Pathogenesis & Underlying Mechanisms**

392 Autoimmune Disorders – Current Concepts and Advances from Bedside to Mechanistic Insights

Yazisiz, V.; Ongut, G.; Terzioglu, E. & Karayalcin, U. (2010). Clinical importance of

*International Journal of Clinical Practice*, Vol. 41, No. 1, pp. 19-24

antineutrophil cytoplasmic antibody positivity during propylthiouracil treatment.

**21** 

*Scotland, U.K.* 

**The Ectopic Germinal Centre Response in** 

*Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow,* 

The pathological effects of autoimmune diseases on the target tissues can be mediated by autoantibodies, cell-mediated immune responses, or both. It is increasingly evident that some autoimmune diseases previously thought to be essentially T-cell-mediated also have a B-cell component, which may involve direct effects of autoantibody secreted by plasma cells, pro- or anti-inflammatory cytokines secreted by activated effector or regulatory B-cells, or through the highly efficient antigen presentation function of B-cells enabling them to activate CD4+ T-cells and *vice versa.* The number of autoimmune diseases known to be mediated partly or largely through autoantibodies has increased markedly in recent times. Systemic lupus erythematosus (SLE)1, in which the pathology is mediated via Type II & III hypersensitivity reactions involving anti-DNA autoantibodies, has long been known to fall into this category. Many other autoantibodies are produced by these patients, principally against nuclear antigens, but most are not thought to be involved in pathology. Hashimoto's thyroiditis and Graves' disease patients produce pathogenic autoantibodies against thyroid antigens, the latter being a rare example of an activating autoantibody inducing signalling via the thyroid stimulating hormone receptor. Myasthenia gravis patients produce autoantibodies against the acetylcholine receptor (AChR), present on the motor muscle endplates, thereby inhibiting muscle contraction. Anti-SS-A and anti-SS-B (anti-Ro & anti-La) autoantibodies are implicated in congenital heart block in children born to mothers with Sjögren's Syndrome due to transplacental uptake of IgG autoantibodies; autoantibodies against α-fodrin are also believed to be pathogenic in these patients. Rheumatoid arthritis (RA), one member of the group of systemic rheumatic autoimmune diseases that also includes SLE, psoriatic arthritis and the various forms of myositis, has now gone full cycle in views on its pathological mechanisms.

1 Abbreviations: AChR, Acetylcholine Receptor; AID, Activation Induced Cytidine Deaminase; AMC, Arthrogryposis Multiplex Congenita; ARS, Anti-amino acyl-tRNA Synthetase; Bmem, Memory B-cell; CDR, Complementarity Determining Region; DM, Dermatomyositis; EOMG, Early Onset Myasthenia Gravis; FDC, Follicular Dendritic Cell; G.C., Germinal Centre; IBM, Inclusion Body Myositis; IM, Inflammatory Myopathies; LOMG, Late Onset Myasthenia Gravis; MAA, Myositis-Associated Autoantibodies; MAb, Monoclonal Antibody; MIR, Main Immunogenic Region; MSA, Myositis Specific Autoantibodies; PM, Polymyositis; RA, Rheumatoid Arthritis; SLE, Systemic Lupus Erythematosus; TAA, Tumour-Associated Antigen; TIL, Tumour-Infiltrating Lymphocytes; Tfh, Follicular T helper cell;

**1. Introduction** 

UNG, Uracil Nucleotidyl Glycosylase.

**1.1 The B-cell response in autoimmune disease<sup>1</sup>**

**Autoimmune Disease and Cancer** 

David I. Stott and Donna McIntyre
