Systemic lupus erythematosus (SLE) is an autoimmune disease in which organs, tissues, and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes. Ninety percent of patients are women of child-bearing years; people of both genders, all ages, and all ethnic groups are susceptible. Prevalence of SLE in theUnited States is 15 to 50 per 100,000; the highest prevalence among ethnic groups is in African Americans.
Principal terms in immunology Immune response : collective, coordinated response to the introduction of foreign substances Innate immunity: exists before infection, consists of early responses to pathogens, non-specific but against common macromolocules Adaptive immunity: develops later, is highly specific for a certain pathogen, “immunological memory” Leukocytes : mediate innate and adaptive immune responses, located in blood, lymph, lymphoid tissues and organs
Cells of the immune system Innate immunity Phagocytes: neutrophils macrophages Natural killers (NK) Eosinophils Basophils Mast cells Adaptive immunity B lymphocytes T lymphocytes Link Antigen presenting cells, dendritic cells NK-T cells
Cytokines *small secreted proteins, produced in response to pathogens *growth, differentiation and activation of leukocytes during innate and adaptive immune responses *cell-to-cell communication, generally act locally *“messengers” of the immune system * short-lived, biological effects at very low concentrations
Types of cytokines interleukins : between leukocytes Interferons : anti-viral effects growth factors : role in haematopoiesis cytotoxic: tumor necrosis factor chemokines: chemotaxis, movement
IMPORTANT CYTOKINES IL-1, TNF- IL-6, proinflammatory and cytotoxic role IL-2, Th proliferation, NK proliferation and activation IL-4, B cell Ig class switching, Th proliferation and differentiation IL-5, eosinophil proliferation and differentiation IL-10, TGF-β, immunosupression, inhibit effector cell proliferation IFN-γ, B cell Ig class switching, antiviral immunity, macrophage activation IL-12, directs adaptive immunity, activates NK cells
H ΕΙΔΙΚΗ ΑΜΥΝΑ TH1/TH2 TH1 = κυτταροτοξική δράση (cell mediated immunity) IFNs, MHC I, IL-12, APC, TH2= χυμική ανταπόκριση (humoral immunity) B cells, MHC II, APC, MACROPHAGES, TH1
Thus, in SLE, antigens are available; they are presented in locations recognized by the immune system; The antigens, autoantibodies, and immune complexes persist for prolonged periods of time, allowing tissue damage to accumulate to the point of clinical illness.
1.Malar rash Fixed erythema, flat or raised, over the malar eminences 2.Discoid rash Erythematous circular raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur 3.Photosensitivity Exposure to ultraviolet light causes rash 4.Oral ulcers Includes oral and nasopharyngeal ulcers, observed by physician
5.Arthritis Nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion 6.Serositis Pleuritis or pericarditis documented by ECG or rub or evidence of effusion 7.Renal disorder Proteinuria >0.5 g/d or ≥3+, or cellular casts 8.Neurologic disorder Seizures or psychosis without other causes
9.Hematologic disorder Hemolytic anemia or leukopenia (<4000/µL) or lymphopenia (<1500/µL) or thrombocytopenia (<100,000/µL) in the absence of offending drugs 10.Immunologic disorder Anti-dsDNA, anti-Sm, and/or anti-phospholipid 11.Antinuclear antibodies An abnormal titer of ANA by immunofluorescence or an equivalent assay at any point in time in the absence of drugs known to induce ANAs a If ≥4 of these criteria, well documented, are present at any time in a patient's history, the diagnosis is likely to be SLE. Specificity is ~95%: sensitivity is ~75%.
Αντιφωσφολιπιδικό Σύνδρομο (ΣΑΦ) Αντισώματα κατά καρδιολιπίνης % Υγιείς 0,2-9 Συστ. Ερυθηματώδης Λύκος 30-50 – ΣΑΦ 1/3 των αΚΛ(+) Ηλικιωμένοι Manoussakis et al, Clin Exp Immunol, 1987; 69:557 52 Petri M: The Antiphospholipid Syndrome. Asherson et al (Eds) Elsevier 2002;11
Πολυκεντρική μελέτη 1000 ασθενών με ΣΑΦ από την Ευρώπη Γυναίκες: Άνδρες = 5:1 Λευκή φυλή: 98,5 % Μέση ηλικία έναρξης συμπτωμάτων: 34±13 έτη Πρωτοπαθές ΣΑΦ: 53% Δευτεροπαθές ΣΑΦ: 36 % σε συνδυασμό με ΣΕΛ 5 % με υποκλινικό ΣΕΛ 5,9 % με άλλα αυτοάνοσα νοσήματα Καταστροφικό ΣΑΦ: 0,8 %