‘Immune reactions against self-antigens’

Pathologic autoimmunity: defined as

1. Presence of autoimmune reaction

2. Not secondary to tissue damage

3. Absence of other cause of disease

Constitute 1-2% of population

AUTOIMMUNE DISEASES:

ORGAN-SPECIFIC:

Hashimoto’s thyroiditis

Autoimmune hemolytic an

Good-Pauster syndrome

Myasthenia Gravis

Ulcerative colitis

Primary Biliary cirrhosis

SLE

RA

PAN

Systemic sclerosis

Sjögren syndrome

Inflammatory myopathies

MECHANISM OF AUTOIMMUNITY

Immune tolerance is Incapable of developing Immune response

to a specific antigen

Self tolerance:::: is No immunological response towards self

antigens

Self tolerance is necessary to avoid Autoimmunity

Reduced self tolerance Autoimmune diseases

Mechanism of self tolerance: Central / Peripheral

Self Reactive T - Lymphocytes

Anergy Suppression Apoptosis

Peripheral Tolerance

Self Reactive T - Lymphocytes

Genetic Susceptibility

Inflammation

Tissue Injury

Tissue Damage

Systemic Lupus Erythematosus:

“Multisystem disease of autoimmune origin, characterized by a bewildering array of autoantibodies, particularly antinuclear antibodies (ANA’s)”.

Chronic, remitting and relapsing, often febrile illness characterized principally by injury to skin, joints, kidney and serosal membranes.

Predominantly disease of women, M:F=1:9

? Autoimmune Disease

? Type III

Hypersensitivity

1997 revised criteria for SLE:

1. Renal disorder

2. Malar rash

3. Discoid rash

4. Serositis

5. Oral ulcer

6. Arthritis

7. Photosensitivity

8. Hematologic disorders

9. Immunology: Anti-ds DNA, Anti-Sm, Antiphospholipid

10. Neurological disease

11. Antinuclear antibody

R-MD-SOAP-HINA

Presence of 4 or more out of these 11 criteria SLE

Directed against nuclear antigens

4 Categories:

Anti DNA,

Anti Histones,

Antibodies to non histone proteins,

Antibodies to Nucleolar antigens

Detection by Indirect Immunoflouresence

Pattern of nuclear florescence suggests the type of Ab

ANTINUCLEAR ANTIBODIES

ANA- Anti Nuclear Antibodies

ANA is positive in most of the Autoimmune disease

In SLE, detection of ANA is a sensitive test but not specific

APLA (Antiphospholipid antibody syndrome): seen in 40 to

50% of patients with SLE.

PATTERNS OF IMMUNOFLORESCENCE

Homogenous or Diffuse Antibodies to Chromatin,

Histones, Ds DNA

Rim or Peripheral staining Anti Ds DNA (40-60% SLE)

Speckled pattern Anti Sm, Ro, La (RNP)

Nucleolar pattern Systemic sclerosis patients

(Anti DNA Topo)

AUTOIMMUNE DISEASE SPECIFIC ANTIBODY

Systemic Lupus

Erythematosus

1. Anti Ds DNA

2. Anti Sm

Drug induced SLE Anti Histone

Systemic Sclerosis Anti DNA Topoisomerase I

(Scl 70)

Limited Scleroderma Anti Centromere

Sjogren Syndrome Anti SS-A (Ro)

Anti SS-B (La)

Inflammatory Myopathies Anti Jo1

Morphology depends on nature of antibody, tissue involved,

course, duration of disease

Deposition of immune complex **

Acute necrotizing vasculitis

Skin: Erythematous, Maculopapular eruption over malar

eminence-Classical feature.

SLE MORPHOLOGY

SLE- Multi-organ disease:

Joint: Erosion of articular cartilage, swelling, inflammation

CNS: Focal neurological deficits,

Neuropsychiatric symptoms.

Multifocal cerebral infarct.

Heart: “Libman sacks endocarditis”.

Pericarditis,

Lung: Pleuritis, interstitial pneumonitis.

“Lupus Nephritis”

Most common cause of death—renal failure

More of glomerular lesions are seen.

Deposition of Immune complexes in Glomeruli

25 to 30% of SLE kidneys appear normal on LM but 100%

involved when seen on IF, EM

RENAL LESIONS IN SLE

Class I: Normal by LM, IF, EM

Class II: Mesangial Glomerulonephritis

Class III: Focal Glomerulonephritis

Class IV: Diffuse proliferative Glomerulonephritis

Class V: Membranous Glomerulonephritis

WHO CLASSIFICATION OF RENAL LESIONS IN SLE

Present in 40% - 50% of SLE

Ab-directed against anionic plasma-proteins and plasma

protein epitopes.

False positive test for syphilis as cardiolipin antibody used in

Syphilis reacts with these antibodies.

Primary—not associated with SLE

Secondary—associated with SLE.

ANTI-PHOSPHOLIPID AB:

In Vivo: Thrombosis: Hypercoagulable status; THROMBOSIS–

by platelet activation, decreased PGI2 and protein C-

synthesis.

In Vitro: Anticoagulant: interfere with clotting tests: like

APTT.

Recurrent venous and arterial thrombosis– cardiac valvular

vegetations, deep venous ulcers, pulmonary

thromboembolism, pulmonary HT, stroke, bowel infarction

Recurrent Fetal loss (antibody mediated inhibition of t-PA):

required for trophoblastic invasion of uterus.

Effect of Thrombosis:

Therapeutic Approaches of Autoimmune Diseases

Plasmapheresis

Remove circulating antibodies

Short term improvement

Immunosuppression

Steroids

Cyclosporine A