| Sažetak | Autoimuna hemolitička anemija (AIHA) heterogena je skupina bolesti uzrokovana napadom vlastitih protutijela, autoprotutijela, na antigene eritrocita. Dijeli se na primarnu AIHA, nastalu kao posljedica imunološke reakcije, te sekundarnu, nastalu uslijed poremećaja imunološke regulacije. Incidencija AIHA iznosi 1 do 3 slučaja na 100 000 osoba godišnje, a dijagnosticira se direktnim (DAT) i indirektnim (IAT) antiglobulinskim testom. Na temelju dijagnostičkih testova i osobina autoprotutijela, AIHA se dijeli na toplu (wAIHA), hladnu (cAIHA) i miješanu. Nadalje, hladna se AIHA, prema etiopatogenezi, dijeli na bolest hladnih aglutinina (CAD) te sindrom hladnih aglutinina (CAS). Paroksizmalna hladna hemoglobulinurija (PCH) rijedak je oblik autoimune hemolitičke anemije u kojemu se autoprotutijela vežu na eritrocite na niskim temperaturama, a komplement aktiviraju pri visokim temperaturama. Uz aktivaciju sustava komplementa i stvaranje membranskog napadajućeg kompleksa (MAC), hemoliza može biti uzrokovana aktivacijom ADCC mehanizma ili fagocitozom eritrocita od strane makrofaga. Poremećaji gena regulacije imunosnog sustava, infekcije, okoliš, lijekovi i tumorske tvorbe mogući su uzroci nastanka AIHA. Obzirom na heterogenost bolesti i različite imunopatogene mehanizme nastanka AIHA, terapije se mogu uvelike međusobno razlikovati. Prva su linija liječenja glukokortikosteroidi, potom slijede rituksimab, ali i splenektomija. Imunosupresivni lijekovi, ciklosporin, azatioprin ciklofosfamid, čine treću liniju terapije. U tijeku su klinička ispitivanja novih terapija koje uključuju inhibiciju fagocitoze eritrocita (fostamatinib, nipocalimab), inhibiciju Brutonove tirozin kinaze (rilzabrutinib i ibrutinib), inhibiciju proteasoma (bortezomib), anti CD38 monoklonska protutijela (daratumumab, isatuximab), inhibiciju mTOR (sirolimus) i inhibiciju proteina komplementa (ekulizumab, pegcetakoplan, sutimlimab). |
| Sažetak (engleski) | Autoimmune hemolytic anemia (AIHA) is a heterogeneous group of diseases
caused by the attack of endogenous antibodies (autoantibodies) on
erythrocyte antigens. It is divided into primary AIHA, which results from an
immune response, and secondary AIHA, which is caused by disorders of
immune regulation. The incidence of AIHA is 1 to 3 cases per 100,000
people per year, and it is diagnosed by direct (DAT) and indirect (IAT)
antiglobulin tests. Based on the diagnostic tests and the characteristics of
the autoantibodies, AIHA is divided into warm (wAIHA), cold (cAIHA), and
mixed forms. In addition, cold AIHA is subdivided into cold agglutinin
disease (CAD) and cold agglutinin syndrome (CAS), depending on the
etiopathogenesis. Paroxysmal cold hemoglobinuria (PCH) is a rare form of
autoimmune hemolytic anemia in which autoantibodies bind to erythrocytes
at low temperatures and activate the complement system at high
temperatures. With activation of the complement system and formation of
the membrane attack complex (MAC), hemolysis may be caused by
activation of the ADCC mechanism or phagocytosis of erythrocytes by
macrophages. Disorders of genes regulating the immune system, infection,
environment, drugs, and tumor formation are possible causes of AIHA.
Considering the heterogeneity of the disease and the different
immunopathogenic mechanisms of AIHA, therapies may differ widely. The
first line of treatment is glucocorticosteroids, followed by rituximab, but also
splenectomy. Immunosuppressive drugs, cyclosporine, azathioprine, and
cyclophosphamide, make up the third line of therapy. Clinical trials of new
therapies include erythrocyte phagocytosis inhibition (fostamatinib,
nipocalimab), Bruton tyrosine kinase inhibition (rilzabrutinib and ibrutinib),
proteasome inhibition (bortezomib), monoclonal antibodies to CD38
(daratumumab, isatuximab), mTOR inhibition (sirolimus), and complement
protein inhibition (eculizumab, pegcetacoplan, sutimlimab). |
