MHC - Major Histocompatibility complex

The cell-mediated adaptive immune response is regulated by the major histocompatibility complex (MHC). The major role of the MHC is to bind small peptides and to present them to the cell surface where the antigen can be recognised by T cell receptors in the adaptive cell mediated immune system.

 

Up-regulation
MHC-1 as a predictive or diagnostic determinant for inflammatory myopathy. (Salaroli, Baldin 2011) [1]

Here is a very informative article showing how conditional up-regulation of MHC class 1 in skeletal muscle leads to self-sustaining autoimmune myositis. (Nagaraju, Raben, Loeffler et al.. Aug. 2000) [2] It is interesting that this article shows that the upregulation of the MHC 1 appears at least occasionally to predate the presence of proinflammatory cytokines and the lymphocytic infiltration, thus implying that there may be another cause of the underlying MHC1 upregulation, which may in fact be different in different cases - truly ideopathic. I also understand him to say that this upregulation may be a result not only of the type of tissue injury that occurs, but also of the duration of that injury (my emphasis). Note also the article below on humoral response to tissue injury.

Here is a detailed article on how the auto-immune malfunction happens in PM. It Explains the MHC-1 and the CD*+ interaction, etc. together with the latest advances in diagnosis. (Dalakas 2004) [3]

IFN-gamma is involved in the aberrant expression of major histocompatibility complex molecules in the affected muscles of patients with polymyositis-dermatomyositis. (Kalovidouris 1992) [4]

The study of the intensity and pattern of major histocompatibility complex I and II expression in muscle from patients with biopsy-proven idiopathic inflammatory myositis could help us to understand the relationship between the major histocompatibility complex and this autoimmune disease.

Anatomo-pathological findings

Multiple randomized studies of the expression of MHC-I  have been published, one where 120 muscle tissue biopsies were performed wins relevance , all IIM biopsies showed MHC I positivity; 93% showed MHC II positivity. MHC I expression showed a perifascicular pattern. All IBM biopsies were immunopositive for MHC I and II, so the Immunostaining for MHC I and II is a useful adjunctive test in diagnosis and sub classification of IIM. This is just a relationship. (5)

The most common autoimmune muscle disorders include dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myositis (NAM) and sporadic inclusion body myositis (sIBM).

PM and IBM are T cell-mediated disorders where cytotoxic CD8⁺ T cells clonally expand in situ and invade major histocompatibility complex class I expressing muscle fibers.

In inflammatory myopathies muscle biopsy is a crucial diagnostic test. Misinterpretation between inflammatory myopathies and muscular dystrophies with inflammation is known, even for experienced pathologists. MHC I up-regulation is noted in PM and DM. Interstitial and perivascular inflammation in PM were predominantly CD8, in contrast with CD4 and CD8 found on DM. (6). MHC-I up-regulation was seen in all 16 cases of muscular dystrophy with presence of inflammation, so there is a true up-regulation in the cases of muscular dystrophy of inflammatory origin but it was difficult to differentiate the expression of MHC I alone.

Relevance

The relationship between the major histocompatibility complex-I and the appearance of the PM, may be promising in the treatment of this disease, like in the cancer immunotherapy, blocking the immune system could improve treatment response. The immune checkpoints are initiated by ligand–receptor interactions, they can be blocked or modulated, the function of MHC I molecules is to bind peptide fragments derived from pathogens and display them on the cell surface for recognition by the appropriate T cell, this check point could be blocked too. (7)

The characterization of patients into subgroups based on autoantibody profiles seems to be a promising way to learn more about the specificities of the immune reactions

Article contributed by Dr. JOSE PEREIRA, MD

Footnotes:

1. Roberta Salaroli, Baldin E,Papa V,Rinaldi R,Tarantino L. Validity of internal expression of the major histocompatibility complex class I in the diagnosis of inflammatory myopathies.. . Journal of clinical pathology , DOI:10.1136/jclinpath-2011-200138, 2011 as found at VIEW

2. Kanneboyina Nagaraju, Rabin N,Loeffler L,Parker T,Rochon P,Le E,Danning C. Conditional up-regulation of MHC class I in skeletal muscle leads to self-sustaining autoimmune myositis and myositis-specific autoantibodies. PNAS, 9209–9214, doi: 10.1073/pnas.97.16.9209, 2000 as found at VIEW

3. Dalakas MC, . Inflammatory disorders of muscle: progress in polymyositis,dermatomyositis and inclusion bodymyositis. Curr Op in Neurol , 17:561–567, 2004 as found at VIEW

4. Kalovidouris, AE, . The role of cytokines in polymyositis: interferon-gamma induces class II and enhances class I major histocompatibility complex antigen expression on cultured human muscle cells.. . J Lab Clin Med, 120(2):244-51, 1992 as found at VIEW

5. Das, Leena, Peter C. FRCPA,FRACP†; Manavis,Jim BSc (Hons)†; Limaye,Vidya S. MBBS,FRACP,PhD‡,Blumbergs P,Manavis J,Limaye V. Major Histocompatibility Complex Class I and II Expression in Idiopathic Inflammatory Myopathy. Applied Immunohistochemistry & Molecular Morphology: , December 2013 - Volume 21 - Issue 6 - p 539–542, 2013 as found at VIEW

6. Madhu, Nagappa, Nalini A. Major histocompatibility complex and inflammatory cell subtype expression in inflammatory myopathies and muscular dystrophies. Neurol India 2013, 61:614-21, 0 as found at VIEW

7. Drew, M. Pardolli, . The blockade of immune checkpoints in cancer immunotherapy. Nature Reviews Cancer, 12, 252-264, 2012 as found at VIEW