AUTOIMMUNITYPRESENTER: KEAGAN KIRUGOSUPERVISOR: DR.J.NYAGOL

GUIDELINES•Definition•Triggers•Various antibodies and their respective diseases•Diagnosis of the autoimmune diseases•Treatment

DEFIt is an inadequately controlled, inappropriately targeted immune response against host cells and tissue due to failure of self-tolerance.

TRIGGERSClassified into genetic, environmental and non-genetic host factors

Genetic predisposing factors1. Presence of certain major histocompatibilty

II(MHC II) alleles: The following is a table showing the human leucocyte antigens with their respective disease association

HLA DISEASE

HLA DR2 Systemic lupus erythematosus(SLE)

HLA DR3 Sjorgen’s syndrome, myasthenia gravis, diabetes mellitus type I(Type I DM)

HLA DR4 Rheumatoid arthritis, DMtype I, pemphigus vulgaris

HLA DRB1 Ulcerative colitis

HLA DR7 Crohn’s disease

HLA DQ4 Crohn’s disease

2. Escape of autoreactive lymphocytes:This is due to the negative selection mechanism of eliminating immature lymphocytes reacting to self antigens strongly may be not be fully functional.

3. Lack of regulatory T lymphocytes (T-regs)

Environmental factors

1.Crossreactive antigens: Presence of epitopes within the pathogen that cross-react with self antigen.

PATHOGEN TISSUECROSSREACTIVITY

DISEASE

Streptococcuspyogenes

Heart valves Rheumatic heart disease

Campylobacterjejuni, Cytomegalovirus, Influenza

Peripheral nerves Gullain-Barre Syndrome

2. Escape of sequestered antigens: Lymphoid cells are not exposed to some of the self-antigens during their maturation in the thymus since these antigens are confined in specialized tissue such as testes, brain or the eye. Release of the sequestered antigens due to trauma, surgery or infection may trigger an autoimmune response.

3.Chemical agents. For example hydralazine, procainamide and isoniazid are associated with increased antinuclear antibodies which are the autoantibodies in systemic lupus erythromatosus. The picture above shows the clinical manifestation.

Non-genetic host factors

1. Immunodeficiency: Lack of appropriate immune response required to clear a pathogen may lead to perpetual host immune system stimulation leading to autoimmunity e.g. IBD

2. Hormonal influences: SLE is 10x higher in females than males. Oestrogen triggers SLE while androgens and progestins suppress the immune response.

DISEASE TARGET ANTIBODY TO

Hashimoto’s thyroiditis Thyroid Thyroglobulin, thyroid peroxidase

Pernicious anaemia Red cells Intrinsic factor

Addison’s disease Adrenal Adrenal cells

Premature onset menopause

Ovary Steroid producing cells

Male infertility Sperms Spermatozoa

Insulin dependent diabetes

Pancreas Pancreatic islet cells

Myasthenia gravis Muscle Muscle acetylcholine receptor

Goodpasture’s syndrome

Kidney, lung Renal and lung basement membrane

Pemphigus Skin Desmosomes

Phacogenic uveitis Lens Lens protein

DISEASE TARGET ANTIBOBY TO

SLE Skin, joints, kidneys etc DNA, RNA, nucleoproteins

Rheumatoid arthritis Joints IgG

Vitiligo Skin Melanocytes

Sjogren’s syndrome Secretory glands Duct tissue

Ulcerative colitis Colon Colon lipopolysaccharide

Idiopathic neutropenia Neutrophils Neutrophils

Primary biliary cirrhosis Liver Mitochondria

DIAGNOSIS

A good history followed by a physical exam Routine laboratory test showing increases

erythrocyte sedimentation test or c-reactive protein should be treated with a high index of suspicion

This should be followed by specific serological assays to detect autoantibodies. This is most appropriate for systemic autoimmune diseases e.g. SLE

Localised autoimmune disease are best diagnosed by immunoflourescence of biopsy specimens

TREATMENTReducing inflammation is the mainstay of treatment.

Drugs administered are Corticosteroids Blockers of:

-TNF integrins IL-1 B cell depletion (anti-CD20)

In extreme cases, administer cyclosporine, large doses of IgGs and do plasmaphoresis.Supportive treatment where necessary: IV fluids, analgesics, antipyretics

SLE

A systemic autoimmune diseaseEpidemiologyFemale: male 10:1Peak ages is between 20 and 40 yearsClinical features

Malar rash, lymphadenopathy, arthralgias, fever, fatigue and will often complain of recurrent flu-like illness

With disease advancement pleurisy, pericarditis, hair loss

Laboratory diagnosisIncreased ESR and C-reactive proteinEvidence of kidney damage by red blood cells

and protein in urinePresence of autoantibodies in serum especially

antinuclear antibody

REFERENCES

2nd year immunology notes by Dr. Lyle McKinnon given in 2012

www.wikipedia.org//autoimmunity last modified on 8th March 2013

www.lupusinternational.com copyright 2011 Roitt Roitt’s Essential Immunology published

in 1995 www.google.com//systemic lupus

erythromatosus

THANK YOU, SHUKRAN.