Autoimmunity

Autoimmunity

conditions in which damage to organs/tissue results from the presence of autoantibody/autoreactive cells

SLE manifestations

arthritis

erythematous skin rash

nephritis

neuropsychiatric

hematologic abnormalities

cardiac abnormalities

fatigue, weight loss, malaise, fever, anorexia

SLE lab features

presence of ANAs, circulating immune complexes, decreased complement (C3 & C4) levels, cyoglobulins, circulating anticoag & nonspecific elevation of IgG levels

Fluorescent ANA (Indirect immunoflrescence)

- most widely used and accepted because of high sensitive

- screening is done: 1:40 or 1:80 dilution of px serum

- titer of > or equal 160 is generally considered to be clinically significant

Homogenous/diffuse

uniform staining of the entire nucleus

Peripheral/Rim

greater staining intensity surrounding the nucleus

Speckled

discrete, fluorescent specks throughout the nuclei

Nucleolar

prominent staining of the nucleoli

Centromere

numerous discrete speckles (46 speckles) are seen in the nuclei

Anti-dsDNA

Staining pattern: homogenous/diffuse, peripheral/rim

Significance: active stage of SLE

Gold standard: IFA staining of Crithidia luciliae

Anti-DNP (deoxynucleoprotein)

Staining pattern: homogenous/diffuse, peripheral/rim

Significance: appearance of LE cells, found in 90% untreated SLE

Anti-Smith/Anti-Sm

Staining pattern: coarsely speckled

Significance: diagnostic of SLE

Anti-RNP

Staining pattern: coarsely speckled

Significance: SLE, RA, Sjorgen's syndrome, mixed connective tissue disease

Anti-histones (nuclear proteins)

Staining pattern: homogenous/diffuse

Significance: drug-induced lupus

Anti-Ro (SS-A)

Staining pattern: finely speckled

Significance: cutaneous/neonatal SLE

Anti-La (SS-B)

Staining pattern: finely speckled

Significance: SLE and Sjogren's syndrome

Anti-nucleolar RNA

Staining pattern: nucleolar

Significance: SLE, Sjogren's syndrome, Systemic sclerosis

Anti-centromere

Staining pattern: discrete, speckled

Significance: SLE, mixed connective tissue disease, CREST syndrome

Rheumatoid factor (IgM), Anti-CCP (cyclic citrullinated peptide)

Rheumatoid Athritis

Anti-thyroglobulin; anti-microsomal

Hashimoto's thyroiditis (HYPOTHYROIDISM)

Anti-TSHr; anti-microsomal

Grave's disease

Anti-islet cells

Type I DM (insulin-dependent/juvenile)

Anti-MBP (myelin basic protein)

Multiple Sclerosis

Anti-acetylcholine receptor

Myasthenia gravis (HL-B8) - muscle weakness

Anti-glomerular basement membrane

Goodpasture's syndrome - glomerulonephritis

Anti-mitochondrial

Primary Biliary Cirrhosis - obstruction of bile duct

Anti-smooth muscle

Chronic active hepatitis - autoimmune hepatitis

Anti-parietal cells

Pernicious anemia (Vit. B12 deficiency)

Anti-salivary/lacrimal glands

Sjorgen's syndrome

Anti-centromere

Scleroderma/CREST - thickening of skin/tissue

Primary Immunodeficiencies (PID)

inherited dysfunctions of immune system

(PID) Category 1: (SCID) Severe Combined Immunodeficiency

- most serious of the congenital immunodeficiencies

- present in early infancy; life span: 2 YEARS MAX

(PID) Category 1: Purine-Nucleosidde Phosphorylase Deficiency

- decreased number of T cells due to accumulation of deoxyguanosine triphosphate, a toxic purine metabolite

- moderate to severe CMI

- normal to mildly impaired HI

(PID) Category 2: Wiskott-Aldrich Syndrome (WAS)

- smallest platelets

- triad: immunodeficiency, eczema, thrombocytopenia

- lethal in childhood bc of infx, hemmorhage, or malignancy

(PID) Category 2: DiGeorge anomaly/Congenital Thymic Aplasia

- zinc deficiency

- thymus development abnormality

- quantitative defect in T cells

(PID) Category 2: Ataxia-Telangiectasia (AT)

- cerebral ataxia (involuntary muscle movements)

- telangiectasias (capillary swelling)

- abnormal GENES produce defect of both humoral & cellular immunity

(PID) Category 3: Transient hypogammaglobulinemia of Infancy

- low lvls of immunoglobulins (5-6 months of age)

- IgG most affected

(PID) Category 3: Selective IgA Deficiency

- most common CONGENITAL IMMUNODEFICIENCY

- susceptible to respiratory of GI infections

(PID) Category 3: Bruton's tyrosine kinase (BTK) deficiency

- X-linked inheritance (males mostly)

- lack circulating mature CD19+ B cells

- lack immunoglobulins of all classes

(PID) Category 3: Common Variable Immunodeficiency

- IgA & IgG deficiency

- spuelike syndrome & malabsorption

(PID) Category 3: Isolated IgG subclass deficiency

- most common: IgG4

- least: IgG1

(PID) Category 5: Chronic Granulomatous Disease (CGD)

- defective bacterial digestion (catalase + bacteria)

- X-linked or autosomal recessive

- inability to produce superoxide

- defective NADPH oxidase system

Neutrophil Oxidative Burst Assay

measures oxidation to rhodamine by the respiratory burst of the leukocyte

Nitroblue tetrazolium test (NBT)

spx: buffy coat

rgt: Bacterial suspension + NBT dye

(+) result: BLUE FORMZAN ppt

normal: 80-100% blue ppt

CGD:

(PID) Category 5: Leukocyte Adhesion Deficiency

- deficiency of CD18

- abnormal motility/chemotaxis, adhesion, and endocytosis

Plasma Cell Dyscrasia

- overproduction of a single immunoglobulin component (Myeloma protein - M)

Multiple Myeloma

- most serious & common of the plasma cell dyscrasia

- malignant plasma cells (CD38, CD56, CD138)

- presence of Bence-Jones protein in urine ( neg on urine strip, positive on SSA ppt)

- hypercalcemia, renal insufficiency and anemia

- 10% of bone marrow cells

Multiple Myeloma turbidity

ppt @ 40-60C = turbid

redissolves @ 100C = no turbidity

Waldenstrom macroglobulinemia

- malignant proliferation of IgM producing plasma cells

- HYPERVISCOSITY due to obstruction of blood vessels

- elevated serum monoclonal protein (macroprotein or IgM paraprotein) that migrates in the gamma region during SPE

Cryoglobulins

precipitate at cold temperatures and can occlude small vessels in the extremities in cold weather