ANA Testing Carrie Marshall 1/18/08 1

Systemic Lupus Erythematosus Azami Ahad.MD Rheumatologist 92/9/30

What is SLE? Prototypic autoimmune disease- loss of immune distinction between self and foreign Combination of a genetically susceptible individual exposed to an environmental trigger Tissue damage occurs by the deposition of autoantibodies in target tissues triggering inflammation.

Demographics of SLE 10/1 prevalence in females versus males 3-4/1 prevalence in African Americans and Hispanics compared to Caucasians Occurs in up to 1% of young black women and is one of the leading causes of natural death in this group Incidence has more than doubled in the last 20 years Morbidity and mortality is markedly higher in African Americans and Hispanics compared to Caucasians

Immune system alterations in SLE T cell abnormalities B cell abnormalities and autoantibody production Monocyte and macrophage abnormalities Defect in immune regulation Abnormality in apoptosis

SLE IMMUNOLOGY Anti-DNA Anti- SSA Anti-SSB Anti-RNP Anti- DNA

PATHOPHYSIOLOGY Prototype multi-system autoimmune disease Immune complexes & auto-antibodies Always consider drug induced lupus: hydralazine phenytoin  anti-histone antibodies minocycline Spectrum: arthralgias, rash, ANA  multisystem dysfunction Fluctuating course with periods of quiescence Spontaneous remission in 20%

Wallace in Arthritis and Allied Conditions, 13th Ed V2, p1319, Brain Salivary, Parotid glands Thyroid Heart, Lungs Serous linings of Heart, Lungs, GI tract Kidneys Special Complications of Pregnancy Skin Organ-threatening Non organ-threatening Joints Blood Vessels And Blood Cells Wallace in Arthritis and Allied Conditions, 13th Ed V2, p1319, Koopman, ed

SCENARIOS “The Dwindles”: fatigue, muscle/joint pain Unexplained single organ disease Skin disease: Discoid lupus Subacute cutaneous lupus (anti-Ro/SSA antibody) Pleural/pericardial effusion Young stroke Nephrotic syndrome  ARF  CRF Complicated pregnancy: Multiple miscarriages Intra-uterine growth retardation (IUGR) Pregnancy induced hypertension/eclampsia

SCENARIOS Unexplained multi-organ disease Fever of Unknown Origin (FUO) Pulmonary renal syndrome Multi-organ dysfunction/failure Unexplained laboratory abnormalities Hemolysis Leuko-/lymphopenia Thrombocytopenia Hypoalbuminemia ANA +

Malar rash- note nasolabial sparing

Malar rash with discoid features

Malar rash again with nasolabial sparing

Lupus rash in sun exposed areas (photosensitivity)

Lupus alopecia

Vasculitic rash of the hand in lupus

Subacute cutaneous lupus associated with anti-Ro antibodies

Rash in neonatal lupus- will fade as mom’s antibodies are cleared

Vesicular rash from lupus- lupus can do anything in the skin

Lupus band test- IgG deposition at the dermal/epidermal interface

Oral ulcers in a patient with lupus- note hard palate location

Jaccoud’s arthropathy in lupus- joint deformities are reducible-no erosions

Libman Sachs endocarditis in lupus- sterile deposits usually mitral valve

Systemic Lupus Erythematosus: Renal Histology Normal Light Microscopy, but Immunoglobin or Complement Protein Deposits Present Mesangial Lupus Nephritis Mild Focal Glomerulonephritis Diffuse Proliferative Glomerulonephritis Membranous Glomerulonephritis Interstitial and Tubular Nephritis ACR

Renal Disease in Lupus Renal disease is the leading determinant of morbidity and mortality in SLE Vast majority of renal disease is WHO Class III or IV proliferative nephritis African Americans with lupus nephritis have a 5-10 fold increased risk of renal failure compared to age/sex matched Caucasians despite similar treatment

Glomerular staining with anti-IgG indicating immune complexes

SLE: Nervous System Disorders Seizures Ataxia Headache Rigidity, Tremor Stroke Syndromes Chorea Transverse Myelitis Aseptic Meningitis Coma Psychiatric Disorders Dementia ACR

Choroid bodies in a patient with SLE

Retinal vasculitis with hemorrhage- associated with CNS lupus

Large infarct in a patient with CNS lupus

LE cells are dropped and anti-phospholipid antibodies added

Review of antibody structure- emphasize importance of Fc complement fixation and Fc Receptor binding

Laboratory Evaluation of SLE Screening test is the ANA (antinuclear antibody) which is positive in >95% of patients with SLE Four patterns- speckled, homogeneous, rim and nucleolar (seen in scleroderma) The speckled pattern is associated with antibodies to Sm, RNP, Ro and La The rim pattern is associated with antibodies to double stranded DNA

Laboratory (continued) Antibodies to Sm are felt to be specific for SLE- if you have them you have lupus Anti-RNP antibodies are seen in lupus and mixed connective tissue disease Anti-Ro and La antibodies are seen in SLE and in Sjogrens syndrome

Laboratory Monitoring of Disease Activity The serum tests useful for following lupus disease activity are anti-dsDNA antibodies and complement levels (C3-C4 or CH50). In some patients anti-dsDNA antibody levels parallel disease activity With active disease complement proteins are consumed thus serum C3, C4 and CH50 decrease

Laboratory Monitoring (Continued) CBCs are useful to monitor for development of Coombs positive hemolytic anemia as well as immune neutropenia and immune mediated thrombocytopenia Urine analysis will demonstrate increased proteinuria and an active sediment (RBCs, WBCs and casts) with active lupus nephritis All of these measures should improve with therapy