Diseases of the autoimmune system

Dr. Fardan QadeerDept. Of PathologyCIMS and H, Lucknow

SLESystemic Lupus Erythematosus

It is an autoimmune disorder which involves multiple systems of the body

Incidence: it is a fairly common disease and the prevalence is as high as 1 in 2500

Gender: It has a strong female predisposition, female is to male ratio is as high as 9:1

Age: it can occur at any age group but usually common in 2nd to 3rd decade of life

Etiology: The exact etiology of the disease is unknown but various factors are attributed to the development of autoimmunity

•Genetic factors:▫A high rate of concordance in monozygotic

twins (25%)▫Positive association of disease with class 2

HLA gene particularly HLA-DQ

•Environmental factors:▫Ultraviolet radiation (sun exposure)

exacerbates the lesion▫Drugs: certain drugs like procainamide and

hydralazine may lead to development of SLE like features

▫Role of estrogens can be attributed to the higher incidance of disease in females

The fundamental defect in SLE is failure to maintain self-tolerance

•As a result of this a large number of auto antibodies are produced which cause tissue destruction by two mechanism▫Type 2 hypersensitivity: characterised by

formation of antibodies against blood components and resulting in haematological derangement

▫Type 3 hypersensitivity: immune complex get deposited in different tissues resulting in systemic resposes

Pathology: The disease is characterised by formation of various antibodies

• Antinuclear antibodies(ANA): these are antibodies against common nuclear antigen that include both DNA and RNA

• Antibodies to Double stranded DNA (anti-dsDNA) and single stranded DNA (anti-ssDNA) are most specific

• Antibodies to smith antigen(anti-SmAg) are also formed which is a part of ribonuleoprotein

• Anti ribonuleoproteins(anti-RNP) antibodies • Anti histone antibodies• Anti nucleolor antibodies• Anti phospholipid antibodies

•Renal lesions: kidney involvement is one of the most important feature of SLE

▫It commonly involves the glomeruli however tubules and interstitium may be affected

▫It is due to depostion of immune complexes in the kidney and subsequent destruction

Extensive sub endothelial deposition of immune complexes ‘wire loop lesion’ and marked cellularity

•Small Blood vessels: Small arteries and arterioles are involved. It is characterised by necrosis and immune complex deposition

•Skin: There is liquifactive degeneration of the basal layer of the epidermis and deposition of immune complexes at the dermo epidermal junction

•Cardiac lesions (Libman Sacks endocarditis) characterised by presence of vegitations on the mitral and tricuspid valves. It can also cause pericarditis.

•CNS: involvement due to formation of thrombus in the vessel walls caused by ANA deposits. It leads to microinfarcts and subsiquent neurological deficit.

Clinical Features• Malar rash:

Characterised by erythematous and maculopapular eruptions over the malar eminance and bridge of the nose

• Discoid rash • Photosensitivity• Pain less oral or oropharyngeal ulcers• Arthritis• Serositis: Pluritis and Pericarditis • Renal disorders: Renal failure in advanced disease

is the most important cause of death Persistant proteinuria >0.5 gm/dl Presence of cellular cast

•Neurological involvement: Seizures Psychotic Manifestations Focal Neurological deficit

• Hematological features Anemia and reticulocytosis Leucopenia (<4000/mm3) Thrombocytopenia

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Laboratory Diagnosis

• LE cells: It was the first diagnostic test for SLE. It is based on the principal that the ANAs cannot penetrate the intact cells hence the cell nucleus is exposed to bind the ANA resulting in formation of a homogenous mass called as LE body

• This mass is further engulfed by phagocytic leucocytes (polymorphs and monocytes) to form a LE cell

• This is positive in 70% cases of SLE only

•Antibody titre: It is more reliable than LE cells immunofluorescence test is positive in almost 100% cases▫Anti DNA antibodies▫Anti Smith antibodies▫Ant nucleolar antibodies

•Supportive evidances▫Proteinuria▫MRI brain showing microinfarct▫Evidance of Pleural effusion on X Ray▫Evidance of valvular lesions on 2D Echo