Classification of autoimmune diseases

The classification is based on the number of organs involved

-  Organ specific autoimmune diseases affect a single organ or tissue including  Hashimoto’s thyroiditis, Graves disease, 1^o  myxedema, Diabetes, chronic atropic gastritis, Myasthenia gravis

-  Organ nonspecific autoimmune diseases affect many organs and tissues including

•  Systemic lupus erythematosus 

•  Rheumatoid arthritis                               

•  Systemic sclerosis                                    

•  Dermatomyositis                                     

•  Polymyositis

•  Polyarteritis Nodosa                                 

•  Sojourn’s syndrome                                

Here, only SLE (a prototype of autoimmune diseases) is given as an illustration.

 Systemic lupus erythematosis (SLE)

-  Systemic lupus erythematosis is a classic prototype of non-organ specific autoimmune disease characterized by a bewildering array of autoantibodies particularly antinuclear antibodies (ANAS).

-  It is a chronic remitting and relapsing often-febrile illness characterized principally by injury to the skin, joints, kidney and serosal membranes.  Each and very part of the body may be affected. It is common among women of child bearing age and a female to male ratio of 9:1, pick on set 2^nd  to 4^th  decade

Etiology and pathogenesis

-  The fundamental defect in SLE is a failure of regulatory mechanism that sustains self-tolerance.

-  The cause of SLE remains unknown but it appears to be a complex disorder of multi-factorial origin resulting from interactions including:

1. Genetic factors

Increased familial risk, 24% concordance in monozygotic twins (1-3 in dizygotic) defects in early complement components (C2 or C4) etc. MHC regulates production of specific auto-antibodies

2. Hormonal factors

Estrogens confer increased risks (10 times more common in females than males) that accelerate during pregnancy and menses. Androgens however, confer decreased risk 

3.  Environmental factors 

Drugs such as hydralazine, pencillin etc induce SLE – like illness ) in which all acting in concert to cause activation of helper T-cells  and B-cells that results in the secretion of several species of autoantibodies.

Ultraviolet rays

Emotional stress

Surgery

4. Immunologic factors

i)  B cell hyperactivity with hypergammaglobulinemia  

ii) Autoantibodies present with reactivity to DNA, RNA, or phospholipids thus, antinuclear

anti bodies (ANA) are the ones that are directed against several nuclear antigen grouped

into four categories

  1.  Antibodies to DNA

  2.  Antibodies to history

  3.  Antibodies to non-histone proteins bound to RNA

  4.  Antibodies to nucleolar antigens

-  ANAs is virtually positive in every patient with SLE i.e sensitive but it is not specific (other autoimmunity positivity. Regardless of the exact sequence by which autoantibodies are formed, they are clearly  the mediators of tissue injury. Type III hypersensitivity reaction is responsible for most visceral lesions.  DNA – anti – DNA complexes can be detected in the glomeruli and small blood vessels. Autoantibodies against red cells, white cells and platelets mediate their effects via type II hypersensitivity.

-  In tissues, nuclei of damaged cells react with ANAs, lose their chromatin pattern, and become homogenous to produce so – called lupus erythematous (LE) bodies or hematoxylin bodies.  Related to this phenomenon is the LE cell, which is readily seen, in vitro. Basically, the LE cell may phagocyte leukocytes (neutrophiles or macrophages) that has engulfed the denatured nucleus of an injured cell.

Serum complement levels often decreased due to immune mediated compliment consumption It is mostly IgG type, lesser extent of the IgM type

Clinic pathologic features

-  Typically the patients young woman with a butterfly rash over the face

-  Generally the course of the disease is varible and almost unpredictable

-  ANAs can be found in virtually 100% of patients but, not specific

-  The detection of antibodies against double stranded DNA and Sm antigen are virtually diagnostic of SLE

-  Chronic discoid lupus erythmatosis is a disease where its skin involvement may mimic SLE.

-  SLE may affect almost any organ system in variable combinations; this vast heterogenicity in clinical presentation requires a clinical index of suspicion followed by laboratory confirmation. Thus, criteria for the diagnosis of SLE are coined such as molar rash, photosensitivity, oral ulcer, arthritis, renal disorders, hematological disorder, immunologic disorder and antinuclear antibody.

-  A person is said to have SLE in any four or more of the criteria are present serially or simultaneously.

-  Morphologic changes in SLE are also extremely variable. The most characteristic lesions result from the deposition of immune complexes found in the blood vessels, kidneys, connective tissue and skin. Acute necrotizing vasculitis of small arteries and arterioles is characterized by fibrinoid necrosis.

-  Kidney: 60 – 70% involvement by SLE. Anti–dsDNA (60-90%associated with nephritis

   WHO morphologic classification of the renal lesions of SLE:

  Class I Normal light etc microscopy

II Mesengial glomerulonephritis

III focal proliferative glomerulonephritis

IV diffuse proliferative glomerulonephritis

V membranous glomerulonephritis

-  Skin: Acute lesions  “butterfly” rash (50%) where histology shows liqufactive degeneration of the basal layer of the epidermis. Sunlight exposure incites or accentuates the erythema. Chronic lesion: Descoid ( plaques with scales, scarring with central atrophy)

- Joints:  Arthralgia or  non erosive synovitis (unlike rheumatoid arthritis) with little deformity

-  CNS: Neuropsycatric manifestations including seizures, (focal or generalized), psychosis and organic brain syndrome.

- Serositis - Acute, subacute or chronic inflammations of the serosal linings pluritis (30-60%), pericarditis (20-30%), peritonitis (60%)

-  CVS - Myocarditis leading to arrhythmias, congestive heart failures etc. Non-bacterial varrucous endocarditis (Libbman sacks endocarditis) is a warty deposition of valvular walls. Accelerated coronary atherosclerosis with evidence of angina pectoris and myocardial infection.

- Spleen - is moderately enlarged with focal hyperplasia

-  Lungs -Pleuritis and pleural effusion are the most common pulmonary manifestations.

References

Bezabeh ,M. ; Tesfaye,A.; Ergicho, B.; Erke, M.; Mengistu, S. and Bedane,A.; Desta, A.(2004). General Pathology. Jimma University, Gondar University Haramaya University, Dedub University.