Pathology: Rheumatic/Autoimmune

1. Transplant rejection (hyperacute, acute, chronic):

From First Aid, BRS Path, and Robbins. Info is somewhat different between First Aid and BRS Path. See Robbins for more info.

• Hyperacute rejection

Ø Ab-mediated due to preformed anti-donor Ab in the recipient.

Ø Occurs within minutes after transplantation.

Ø Ab deposit on the vascular endothelium of the donor organ. Complement fixation occurs, causing a localized Arthus reaction marked by acute inflammation, fibrinoid necrosis of small vessels, and extensive thrombosis.

Ø The surgeon may recognize hyperacute rejection right after the graft is revascularized.

Ø May see this in a previous transplant recipient, multiparous woman receiving a graft from her husband or children who has developed Ab to paternal-Ag shed from a fetus, or in a patient who has received a blood transfusion from a non-HLA identical donor. However, hyperacute rejection is no longer clinically significant since cross-matching involves screening the recipient’s serum for Ab to the donor.

· Acute rejection

Ø Cell-mediated or Ab-mediated, or both.

Ø Occurs within days in the non-immunosuppressed patient, within weeks to years in the immunosupressed patient after immunosuppression is discontinued.

Ø Cell-mediated rejection is characterized by infiltrating lymphocytes and macrophages. When Ab-mediated mechanisms are present, may see evidence of arteritis with thrombosis.

Ø Reversible with immunosuppressants such as cyclosporin and OKT3.

· Chronic rejection

Ø Ab-mediated vascular damage (fibrinoid necrosis).

Ø Occurs months to years after an otherwise successful transplantation.

Ø Histologically see marked vascular fibrointimal proliferation.

Ø Irreversible.

Ø Is becoming more common as immunosuppression is being used to successfully prevent acute rejection.

2. Differences between rheumatoid arthritis and graft-versus-host disease.

Not sure why this is valuable, so I may have missed something in the answer. Info from First Aid, BRS Path, Lange Medical Micro and Immuno, Robbins. See Robbins for more.

• Rheumatoid arthritis: chronic autoimmune inflammatory disorder primarily affecting synovial joints, but also the skin, blood vessels, heart, lungs, and muscles.

Ø Manifestations: Usually involves joints of hands, knees, and feet, MCP and PIP joints (symmetric). Circulating immune complexes (RF-IgG) are believed to underlie many of the extrarticular manifestations of RA: subcutaneous rheumatoid nodules, pleuritis, pericarditis, anemia, vasculitis, lymphadenopathy, neuro abnormalities, and secondary reactive amyloidosis. Systemic symptoms: fever, fatigue, anorexia, weight loss, myalgia.

ü With Felty’s syndrome, may see splenomegaly.

ü With JRA, may also see hepatosplenomegaly and an acute onset marked by fever.

Ø Patients: Common in females.

Ø Treatment: NSAIDs, immunosuppressives, corticosteroids, and other DMARDs.

· GVHD: Grafted immunocompetent cells (CD4+ and CD8+) proliferate in the irradiated immunocompromised host and reject cells with “foreign proteins,” resulting in severe organ dysfunction.

Ø Manifestations: Major symptoms result from involvement of the immune system and the epithelia of the skin, liver, and GI tract. These include a generalized maculopapular rash leading to desquamation in severe cases, jaundice due to destuction of small bile ducts, hepatosplenomegaly, and diarrhea resulting from mucosal ulceration.

Ø Patients: Common in bone marrow transplant recipients because immunocompetent T cells are transplanted and proliferate in the recipient. Can also be seen in transplantation of solid organs rich in lymphoid cells (eg, liver). May also be seen in recipients of non-irradiated blood transfusions. Occurs weeks to months after a bone marrow transplant.

Ø Treatment: Can be reduced by treating donor tissue with anti-thymocyte Ig or monoclonal Ab before grafting to deplete donor lymphocytes. Can be treated with cyclosporine or tacrolimus, however some of the graft versus host reaction appears to help host engraftment.

3. Psoriasis and sarcoidosis: skin/joint manifestations.

From BRS Path, Cecil’s, Robbins. See Robbins or Cecil’s for more.

	Psoriasis	Sarcoidosis
	Chronic inflammatory process, possibly an autoimmune etiology, of epidermal proliferation and dermal inflammation.	Characterized by noncaseating granulomas, often involving multiple organ systems.
Skin	· Erythematous papules and plaques with characteristic silvery scaling. Lesions are sharply demarcated. Most often involves the extensor surfaces of the elbows and knees, also on the scalp and sacral area. Usually nonpruritic. Pustular psoriasis exists but is rare. · Total body erythema and scale is called erythroderma. · Auspitz’s sign: pinpoint capillary bleeding resulting from lifting of scale from a plaque. · Koebner’s phenomenon: trauma to skin results in new papulosquamous lesions.	· Erythema nodosum: raised, red, tender, nodular lesions generally found on the anterior lower leg. Not due to granulomatous involvement of the skin. · Reduced sensitivity and often anergy to skin test Ag (characteristically neg TB test). · Papules, plaques, nodules, infiltration of old scars, and lupus pernio (chronic, violaceous, often disfiguring lesion affecting the nose, cheeks, and ears) result from granulomatous involvement of skin.
Joint	· Occurs in 5-7% of psoriasis patients. · Insidious onset and progressive course. · 5 variants w/ different characteristics: 1. Asymmetrical oligoarthritis that may involve large and small joints. May see dactylitis (sausage digits). 2. DIP joint involvement is often associated with nail pitting, onycholysis (separation of nail plate from the bed), subungual hyperkeratosis, transverse ridging, and/or leukonychia. 3. RA-like symmetrical polyarthritis without serum RF or rheumatoid nodules. 4. Psoriatic spondylitis. 5. Arthritis mutilans: destructive, erosive, polyarticular arthritis affecting hands, feet, and spine.	· Joint or juxta-articular pain in up to 1/3 of patients. Often begins in ankles and spreads symmetrically. DIPs are usually spared. Episodes last days to months and usually resolve completely. · Progressive, deforming arthritis is a feature of chronic sarcoidosis.

4. AutoAb and disease associations

From First Aid, Cecil’s, Robbins. I bolded those from First Aid.

Antibody	Disease
ANA	SLE
Anti-ds-DNA	Specific for SLE
Anti-histone	Drug-induced lupus
Anti-ribosomal P	SLE
Anti-PCNA (proliferating cell nuclear Ag)	SLE
Anti-IgG	Rheumatoid arthritis
Anti-PMN	Vasculitis
Anti-c-ANCA (Ag is a serine protease)	Wegener’s granulomatosis
Anti-pANCA (Ag is myeloperoxidase)	Microscopic polyarteritis, Churg-Strauss syn.
Anti-p-ANCA (atypical Ag)	Ulcerative colitis, Crohn’s, primary sclerosing cholangitis
Anti-centromere	Scleroderma (CREST)
Anti-mitochondria	Primary biliary cirrhosis
Anti-gliadin	Celiac disease
Anti-basement membrane	Goodpasture’s syndrome
Anti-epithelial cell	Pemphigus vulgaris
Anti-synthetases	Polymyositis and dermatomyositis
Anti-SRP (signal recognition particle)	Polymyositis
Donath-Landsteiner Ab	Paroxysmal cold hemoglobinuria
Anti-islet cell	Type I diabetes
Anti-parietal cell and intrinsic factor	Autoimmune gastritis