RESUMO
OBJECTIVES: The diagnosis of extrapulmonary tuberculous infections and nontuberculous mycobacterial (NTM) infections is difficult because the symptoms are nonspecific and suitable specimens for bacterial culture are often not available. Recent publications reported the existence of autoantibodies in tuberculous infections. We screened for specific autoantibodies in mycobacterial infections. METHODS: We screened four in 29 patients with active mycobacterial infections and different controls using protein array technology. We could identify autoantibodies against ubiquitin-fold modifier-conjugating enzyme 1 (Ufc1) and pleckstrin homology domain containing, family G (with RhoGef domain) member 2 (Plekhg2) in all four patients. Subsequently, we designed enzyme-linked immunosorbent assays (ELISAs) for the detection of autoantibodies binding to Ufc1 and Plekhg2. RESULTS: Autoantibodies binding to Ufc1 and Plekhg2 were found in 19 of 29 patients (66%) with active mycobacterial infections. In comparison, we found these autoantibodies in one of 31 patients (3%) with successfully treated mycobacterial infections, in three of 40 (8%) HIV-infected patients not receiving combination antiretorviral therapy (cART) and in six of 134 (5%) blood donors. Interestingly, six of eight (75%) patients with HIV-associated B-cell non-Hodgkin lymphoma (B-NHL) at the onset of disease had autoantibodies against Ufc1 and Plekhg2, but none of nine (0%) patients after treatment of HIV-associated B-NHL, none of seven patients with non-HIV-associated B-NHL and 11 of 115 (10%) patients with other malignant diseases had autoantibodies against both proteins. CONCLUSIONS: In view of the high frequency of these autoantibodies, we postulate that they might be of potential use for additional diagnostics for mycobacterial infections, and further studies may shed light on the pathomechanisms of these two autoantibodies.
Assuntos
Autoanticorpos/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Infecções por HIV/imunologia , Infecções por Mycobacterium não Tuberculosas/imunologia , Tuberculose Pulmonar/imunologia , Enzimas de Conjugação de Ubiquitina/metabolismo , Adulto , Idoso , Autoanticorpos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Fatores de Troca do Nucleotídeo Guanina/imunologia , Infecções por HIV/fisiopatologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/fisiopatologia , Análise Serial de Proteínas , Ligação Proteica , Sensibilidade e Especificidade , Tuberculose Pulmonar/fisiopatologia , Enzimas de Conjugação de Ubiquitina/imunologiaRESUMO
Takayasu arteritis (TA) is difficult to diagnose because diagnostic biomarkers have not yet been established. In a previous study, we detected autoantibodies against the human ferritin heavy chain protein (HFC) in the sera of patients with giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR). The aim of this study is to evaluate the frequency of autoantibodies against HFC in TA. We established seven ELISA assays for the detection of autoantibodies against HFC. We used the full-length recombinant HFC expressed in Escherichia coli or one of six different HFC peptides as autoantigens: 1-18Aa (98.8 % purity), 19-45Aa (98.8 % purity), 52-78Aa (98.3 % purity), 79-104Aa (98.8 % purity), 105-143Aa (98.4 % purity) and 145-183Aa (98.5 % purity). We collected sera from 48 patients with TA, 36 patients with systemic lupus erythematosus (SLE), 35 patients with arteriosclerosis, 133 patients with febrile diseases, which are known to generate unspecific autoantibodies, and 50 blood donors, which served as controls. The best results were obtained using the ferritin peptides as antigens. By combining the results from the different ELISAs that detect autoantibodies against the HFC peptides 19-44A, 79-104A and 105-144A, we were able to detect ferritin peptide antibodies in 30/48 (62 %) of the TA patients. The frequency was lower than in early GCA and PMR (previous study showed up to 92 %). Positive results were observed in 0/50 (0 %) of the control blood donors, 10/36 (28 %) of the SLE patients, 4/35 (11 %) of the arteriosclerosis patients and 27/133 (20 %) of the fever patients. Considering the lack of biomarkers for TA, autoantibodies against HFC peptides could act as useful markers for TA.