Lupus Flashcards
Causes of lupus
- Genetics (humans, D)
- Viral infections: retrovitus (humans)
- Drugs, hormones-humans
- Chemicals, cigarette -humans
- UV radiation (UVA, UVB): cutaneous LE (humans, D)
Pathogenesis of lupus
- UV damage to basal cell KCs: increased expression of ICAM-I, expression of cytoplasmic (Ro) or nuclear autoantigens
- Ab against autoantigens attach to KCs: Ab-mediated cytotoxicity (however ANA do not produce the lesions)
- KC injury:
a) release of IL-2 and other lymphocyte attractants: lymphohistiocytic infiltration ; D: many plasma cells)
b) release of IL-1, IL-6, TNF-a: increased B cell activity-increased ANA-increased IgM, immune-complex deposition (they occur after skin lesions)
+ humans: KC apoptosis: KC damage by Ab cytotoxicity → hyperproliferation (increased Ki-67) → increased expression of p53 → down-regulates bcl-2 → apoptosis (humans)
Classification of skin lesions
- LE-nonspecific: no lymphocyte-rich interface dermatitis, basal KC damage
- CLE (lupus-specific): lymphocyte-rich interface dermatitis and basal KC damage:
a) Acute CLE or ACLE (humans): will eventually suffer from SLE;
b) Subacute CLE or SCLE (D, humans): vesicular CLE;
c) Chronic CLE or CCLE (D, humans): DLE (D, humans), chilblain LE (humans), lupus timidus (humans), lupus profundus (humans), exfoliative CLE (D), mucocutaneous LE (D)
Causes of SLE
1) Genetics - DLA-A7;
(negative association with DLA-A1 and DLA-B5);
2) Hormonal factors (H): strong female predisposition humans
3) Environmental factors (D, H)
a) Infections (H): possibly in D and C; Epstein Barr and other viruses -hum
b) Drugs (D, H, H): antibiotics (D), hydralazine (D-ANA induction but no clinical signs, H), primidone (D), propiothiuracil (C), vaccination (D); in vitro they react with DNA or nucleoproteins making them more antigenic
c) UV radiation-UVA, UVB (H, D): nuclear damage to basal cells → nuclear antigen expression on cell surface → Ab and cell-mediated damage
Etiopathogenesis of SLE
1) T cell dysfunction: Lymphopenia
Reduced CD8+ cell percentage and absolute numbers, increased CD4+ cell percentage but reduced absolute numbers, high CD4/CD8 ratio
2) Polyclonal B cell activation
-Autoantibodies (IgA, IgM, IgG): organ-specific and not organ-specific; broadly cross-reactive with other auto-antigens; hyperglobulinemia
a) ANA
b) cytoplasmic: Ro/SSA
c) collagen VII (NC1 domain): bullous SLE
d) Lupus anticoagulants
e) Antiphospholipid antibodies
f) Anti CTLA-4
g) Anti-RBC
h) Anti-IgG (rheumatoid factor): 20%
i) Anti-heparan surfate
3) Cytokines
IL-10: overproduction
Pathogenesis of SLE
1) Immune-complex mediated damage: type III; CIC (75% of D)
2) Direct damaging effect of autoantibodies: to tissues bearing the auto-antigen or cross-reacting antigens
3) Functional effects of autoantibodies: interference with the function of the antigen
4) Additional mechanisms
Deficiencies of complement components: reduced phagocytosis of immune complexes → accumulation in tissues
Name major signs in SLE
a) skin lesions,
b) polyarthritis,
c) hemolytic anemia,
d) glomerulonephritis or proteinuria,
e) polymuositis,
f) leukopenia,
g) thrombocytopenia
Minor signs in SLE
a) FUO,
b) CNS signs including seizures,
c) oral ulceration,
d) lymphadenomegaly,
e) pericarditis,
f) pleuritic
Dg using minor and major criteria for SLE
a) positive ANA plus ≥2 major signs,
b) positive ANA + 1 major + ≥2 minor signs
DLE autoantibdoies
Against BMZ: IgG, IgM, IgA and C3
Anti-ENA: 9%
Anti-Ro: 4%
Diagnostic criteria for GDLE
a) >3 month duration;
b) lesions resembling the human disease: annular or polycyclic plaques with dyspigmentation, scales, comedones and central alopecia;
c) typical histopathology: lymphocyte-rich interface dermatitis with basal cell damage
Treatment of GDLE
a) glucocorticoids + CsA;
b) hydroxychloroquine + tacrolimus;
c) tetracycline-niacinamide ± EFA;
d) sun avoidance (?)
Pathogenesis of VCLE
Mechanism: UV → KCs apoptosis → expression of nuclear antigens → production of antibodies → ADCC → further apoptosis
Targeted Ab in VCLE
Antibodies in the skin: IgG (rare IgM) in KCs (43%) and BMZ (50%)
Circulating Ab in VCLE
ANA test is negative; against extractable nuclear antigens (ENA) in 73%: Ro/SSA, La/SSB, Sm, Sm/RNP, Jo-1 (it is an RNA synthetase)
Target in ECLE
Ig: mainly IgG against BM, hair follicles and sebaceous glands in the skin; circulating IgG against hair follicles and sebaceous glands but not against BM
With wich diease can AA be found
vitiligo
Ab target in AA
a) trichohyaline
b) keratins
+IRS, hair matrix, ORS, hair precortex
Treatment of AA
glucocorticoids, CsA, tacrolimus
minoxidil (H);
CsA in guinea pig;
JAK inhibitors in humans
cryoglobulinemia and cryofibrinogenemia is wich type of hypersensitivity
type II
Classification of cryoglobulins:
- Type I (simple): monoclonal (usually IgM) or light chains (Bence-Jones); lymphoproliferative (e.g. multiple myeloma, B-cell lymphoma) > immune-mediated diseases
- Type II (mixed): SIC of a monoclonal (usually IgM) and polyclonal IgG; autoimmune and connective tissue
- Type III (mixed): SIC of polyclonal IgM and polyclonal IgG; autoimmune, connective tissue, infections
what are Cryofibrinogen:
fibrinogen, fibrin, fibronectin, FDPs
Target of cryoglobulins:
RBC (cold agglutinin disease)
IgM: causing RBC agglutination and skin lesions
IgG: not causing RBC agglutination, not causing skin lesions
cryoglobulinemia and cryofibrinogenemia- causes
D: idiopathic, lead poisoning, multiple myeloma, macroglobulinemia
C: idiopathic, lead poisoning, upper respiratory infection, multiple myeloma
th of cryoglobulinemia and cryofibrinogenemia
- Cause
- Cold avoidance
- Immunosuppressive
- PTX: may also be used prophylactically during cold months
how dg is made for cryoglobulinemia and cryofibrinogenemia
serum (for cryoglobulins) + citrated plasma (for cryofibrinogen) at a pre-warmed syringe and tube (37oC) that is left to clot at 37oC (if done at room temperature cryoglobulins may precipitate during centrifugation) → cooled at 4oC leads to gel formation (wait 4-7 days to form) → rewarming at 37oC redissolves the gel;
measurement of cryoglobulin and cryofibrinogen levels: measurement of serum globulins and of plasma fibrinogen before and after gel formation
What is the patogenesis of graft vs host disease
lymphoid cells from immunocompetent donor to an incompatible recipient that is not able to reject them
-differences in minor histocompatibility antigens
Pathogenesis of GVHD
a) keratinocyte upregulation of ICAM-I, CD44 and MHC II,
b) infiltration of CD8+ cells,
c) production of IL-2, IL-3, IL-4, INF-a and TNF-a by T cells,
d) recruitment of new lymphocytes, NK cells and macrophages,
e) attack of host and donor tissue (perforins, TNF-a)
What are ac signs of GVHD
erythema, icterus, diarrhoea, Gram- infection
What are ch signs of GVHD
exfoliative erythroderma, ulcers, ascites, Gram- infection
Th for GVHD
Leflunomide + prednisolone + CsA
What is the name of localized EBA? And in which species has it been reported
Brunsting- Perry like
_ German short haired pointer 10 moths
