RESUMEN
Beta-hemoglobinopathies become prominent after birth due to a switch from γ-globin to the mutated ß-globin. Haploinsufficiency for the erythroid specific indispensable transcription factor Krueppel-like factor 1 (KLF1) is associated with high persistence of fetal hemoglobin (HPFH). The In(Lu) phenotype, characterized by low to undetectable Lutheran blood group expression is caused by mutations within KLF1 gene. Here we screened a blood donor cohort of 55 Lutheran weak or negative donors for KLF1 variants and evaluated their effect on KLF1 target gene expression. To discriminate between weak and negative Lutheran expression, a flow cytometry (FCM) assay was developed to detect Lu antigen expression. The Lu(a-b-) (negative) donor group, showing a significant decreased CD44 (Indian blood group) expression, also showed increased HbF and HbA2 levels, with one individual expressing HbF as high as 5%. KLF1 exons and promoter sequencing revealed variants in 80% of the Lutheran negative donors. Thirteen different variants plus one high frequency SNP (c.304 T > C) were identified of which 6 were novel. In primary erythroblasts, knockdown of endogenous KLF1 resulted in decreased CD44, Lu and increased HbF expression, while KLF1 over-expressing cells were comparable to wild type (WT). In line with the pleiotropic effects of KLF1 during erythropoiesis, distinct KLF1 mutants expressed in erythroblasts display different abilities to rescue CD44 and Lu expression and/or to affect fetal (HbF) or adult (HbA) hemoglobin expression. With this study we identified novel KLF1 variants to be include into blood group typing analysis. In addition, we provide further insights into the regulation of genes by KLF1.
Asunto(s)
Moléculas de Adhesión Celular/genética , Hemoglobina Fetal/análisis , Factores de Transcripción de Tipo Kruppel/genética , Sistema del Grupo Sanguíneo Lutheran/genética , gamma-Globinas/análisis , Células Cultivadas , Células Eritroides/citología , Células Eritroides/metabolismo , Eritropoyesis , Hemoglobina Fetal/genética , Humanos , Mutación , Polimorfismo de Nucleótido Simple , gamma-Globinas/genéticaRESUMEN
ß-Thalassaemia is one of the most common monogenic diseases with no effective cure in the majority of patients. Unbalanced production of α-globin in the presence of defective synthesis of ß-globin is the primary mechanism for anaemia in ß-thalassaemia. Clinical genetic data accumulated over three decades have clearly demonstrated that direct suppression of α-globin and induction of γ-globin are effective in reducing the globin chain imbalance in erythroid cells hence improving the clinical outcome of patients with ß-thalassaemia. Here, we show that the histone deacetylase inhibitor drug, vorinostat, in addition to its beneficial effects for patients with ß-thalassaemia through induction of γ-globin, has the potential to simultaneously suppress α-globin. We further show that vorinostat exhibits these synergistic beneficial effects in globin gene expression at nanomolar concentrations without perturbing erythroid expansion, viability, differentiation or the transcriptome. This new evidence will be helpful for the interpretation of existing clinical trials and future clinical studies that are directed towards finding a cure for ß-thalassaemia using vorinostat.
Asunto(s)
Inhibidores de Histona Desacetilasas/farmacología , Vorinostat/farmacología , Globinas alfa/biosíntesis , Talasemia beta/tratamiento farmacológico , gamma-Globinas/biosíntesis , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Células Eritroides/efectos de los fármacos , Sangre Fetal/citología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Inhibidores de Histona Desacetilasas/uso terapéutico , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Cultivo Primario de Células , Vorinostat/uso terapéutico , Globinas alfa/análisis , Talasemia beta/sangre , gamma-Globinas/análisisRESUMEN
This is the first report of quadrupole time-of-flight (Q-TOF) mass spectrometric identification of the hemoglobin (Hb) subunits, α, ß, δ and γ peptides, derived from enzymatic-digestion of proteins in the early unknown peaks of the cation exchange chromatography of Hb. The objectives were to identify the unknown high performance liquid chromatography (HPLC) peaks in healthy subjects and in patients with ß-thalassemia (ß-thal). The results demonstrate the existence of pools of free globin chains in red blood cells (RBCs). The α-, ß-, δ- and γ-globin peptides were identified in the unknown HPLC peaks. The quantification and role of the free globin pool in patients with ß-thal requires further investigation. Identification of all types of Hb subunits in the retention time (RT) before 1 min. suggests that altered Hbs is the nature of these fast-eluting peaks. Relevancy of thalassemias to the protein-aggregation disorders will require review of the role of free globin in the pathology of the disease.
Asunto(s)
Cromatografía Líquida de Alta Presión , Subunidades de Hemoglobina/análisis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Talasemia beta/sangre , Talasemia beta/diagnóstico , Adolescente , Adulto , Secuencia de Aminoácidos , Niño , Preescolar , Femenino , Subunidades de Hemoglobina/química , Hemoglobinas Anormales/análisis , Hemoglobinas Anormales/química , Humanos , Masculino , Adulto Joven , Globinas alfa/análisis , Globinas alfa/química , Globinas beta/análisis , Globinas beta/química , Globinas delta/análisis , Globinas delta/química , gamma-Globinas/análisis , gamma-Globinas/químicaRESUMEN
BACKGROUND AIMS: γ-globin expression can be induced by various gene modification strategies, which could be beneficial for hemoglobin (Hb) disorders. To translate promising ideas into clinics, large animal models have proven valuable to evaluate safety and efficacy of the approaches; however, in vitro erythroid differentiation methods have not been established to determine whether they can be modeled in nonhuman primates. METHODS: We optimized erythroid differentiation culture to produce high-level adult Hb from rhesus hematopoietic progenitor cells by using low (LC) or high cytokine concentration (HC) protocols with or without feeder cells. In addition, we established rhesus globin protein analysis using reverse-phase high performance liquid chromatography and mass spectrometry. RESULTS: Robust adult Hb production at protein levels was observed in the LC protocol when feeder cells were used, whereas the HC protocol resulted in higher baseline fetal Hb levels (P < 0.01). We then compared lentiviral transduction of rhesus cells between serum-containing LC media and serum-free StemSpan-based differentiation media, revealing 100-fold more efficient transduction in serum-free differentiation media (P < 0.01). Finally, rhesus CD34+ cells were transduced with lentiviral vectors encoding artificial zinc finger proteins (ZF-Ldb1), which can reactivate γ-globin expression via tethering the transcriptional co-regulator Ldb1 to γ-globin promoters, and were differentiated in the optimized erythroid differentiation method. This resulted in marked increases of γ-globin levels compared with control groups (P < 0.01). DISCUSSION: In conclusion, we developed an efficient rhesus erythroid differentiation protocol from hematopoietic progenitor cells with low fetal and high adult Hb production. Further studies are warranted to optimize gene modification and transplantation of rhesus hematopoietic progenitor cells.
Asunto(s)
Técnicas de Cultivo de Célula/métodos , Terapia Genética/métodos , Células Madre Hematopoyéticas/citología , gamma-Globinas/genética , Animales , Diferenciación Celular , Cromatografía Líquida de Alta Presión/métodos , Proteínas de Unión al ADN/genética , Células Madre Hematopoyéticas/metabolismo , Hemoglobinopatías/terapia , Hemoglobinas/análisis , Humanos , Proteínas con Dominio LIM/genética , Macaca mulatta , Regiones Promotoras Genéticas , Proteínas Recombinantes/genética , Espectrometría de Masas en Tándem , Factores de Transcripción/genética , Transducción Genética , Dedos de Zinc/genética , gamma-Globinas/análisisRESUMEN
Background We aimed to determine whether the discrepancy between haemoglobin A1c values determined by high-performance liquid chromatography and enzymatic haemoglobin A1c measurements in diabetic patients was clinically relevant. Methods We randomly recruited 1421 outpatients undergoing diabetic treatment and follow-up who underwent at least three haemoglobin A1c measurements between April 2014 and March 2015 at our clinic. In 6369 samples, haemoglobin A1c was simultaneously measured by HA-8160 and MetaboLead (enzymatic assay), and the values were compared. Results haemoglobin A1c measurements by high-performance liquid chromatography and enzymatic assay were strongly correlated (correlation coefficient: 0.9828, linear approximation curve y = 0.9986x - 0.2507). Mean haemoglobin A1c (6.8 ± 1.0%) measured by high-performance liquid chromatography was significantly higher than that measured by enzymatic assay (6.5 ± 1.0%, P < 0.0001). During the sample processing, four (0.3%) subjects presented consistently lower haemoglobin A1c values (<0.7%) by high-performance liquid chromatography than those from enzymatic assay. Of these, three had Hb Toranomon [ß112 (G14) CysâTrp]. The fourth had Hb Ube-2 [α68 (E17) AsnâAsp]. One other subject presented consistently higher haemoglobin A1c values (>1%) by high-performance liquid chromatography than those from enzymatic assay and was diagnosed with a -77 (T > C) mutation in the δ-globin gene. These unrelated asymptomatic subjects had normal erythrocyte profiles, without anaemia. Conclusions We showed that haemoglobin A1c values measured by high-performance liquid chromatography were significantly higher than those measured by enzymatic assay in diabetic subjects. However, when an oversized deviation (>0.7%) between glycaemic control status and haemoglobin A1c is apparent, clinicians should check the methods used to measure haemoglobin A1c and consider the possible presence of a haemoglobin variant.
Asunto(s)
Artefactos , Diabetes Mellitus/diagnóstico , Hemoglobina Glucada/genética , Hemoglobinas Anormales/genética , gamma-Globinas/genética , Adulto , Anciano , Cromatografía Líquida de Alta Presión/estadística & datos numéricos , Diabetes Mellitus/sangre , Pruebas de Enzimas/estadística & datos numéricos , Femenino , Expresión Génica , Hemoglobina Glucada/análisis , Hemoglobinas Anormales/análisis , Humanos , Masculino , Persona de Mediana Edad , Mutación , Pacientes Ambulatorios , Control de Calidad , Sensibilidad y Especificidad , gamma-Globinas/análisisRESUMEN
Wear testing of total joint replacement (TJR) is mandatory in preclinical testing before implantation of TJR into the human body. Testing is governed by current international standards that recommend bovine serum (BS) as a lubricating fluid to replace synovial fluid (SF). Recently, the use of BS has been criticized because of differences in content, fluid characteristics, and nonhuman origin. As a result, a more realistic lubricant mimicking SF is needed. To define SF composition, we analyzed SF obtained during revisions of total hip and knee arthroplasties and compared it with SF obtained during primary arthroplasties and from patients without TJR. Samples were acquired from 152 patients. We found that the median total protein concentration for all SF was 36.8 mg/mL, which is significantly higher than concentrations currently recommended by the ISO standards. The γ-globulin concentration was significantly higher and the phospholipid concentration significantly lower in patients with revision of TJR compared with patients without TJR. No significant difference was found in hyaluronic acid concentration and viscosity among the groups. Our results support the need to improve the definition of a more clinically relevant wear testing lubricant in the ISO standards. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1422-1431, 2017.
Asunto(s)
Materiales Biomiméticos/química , Lubricantes/química , Fosfolípidos/análisis , Líquido Sinovial/química , gamma-Globinas/análisis , Adulto , Anciano , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fosfolípidos/metabolismo , Líquido Sinovial/metabolismo , gamma-Globinas/metabolismoRESUMEN
Autoantibodies in chronic demyelinating neuropathies have been explored for several years. Recently, the peptides in the nodes of Ranvier have been the focus of attention in finding targets of autoantibodies. Until now, the most popular autoantibodies have been contactin-1 and neurofascin-155 for chronic demyelinating polyradiculoneuropathy (CIDP), GM1-ganglioside for multifocal motor neuropathy, and myelin-associated glycoprotein for polyneuropathy associated with monoclonal gammopathy of unknown significance. IgG is restricted to the IgG4 subtype in CIDP, indicating anti-inflammatory mechanisms related to the functional modification of the nodes of Ranvier. The clinical characteristics are also correlated with the presence of each of the autoantibodies, indicating the importance of auto-antibody screening in the development of suitable therapeutic strategies for each patient.
Asunto(s)
Autoanticuerpos/inmunología , Polineuropatías/inmunología , Enfermedad Crónica , Humanos , gamma-Globinas/análisisRESUMEN
BACKGROUND: A few children with acute or chronic liver disease display histological features compatible with autoimmune hepatitis, but lack specific serological markers. AIM: To describe features, management and outcome of childhood seronegative autoimmune hepatitis. METHODS: From 1988 to 2010, 38 children were included under the following criteria: negative virological studies, no serum autoantibodies, exclusion of other causes of liver diseases, and liver histology compatible with autoimmune hepatitis. RESULTS: Four groups were identified: (1) 12 with increased serum gamma globulin concentrations; (2) 10 with normal or low serum gamma globulins and no combined blood disease; (3) 10 with combined aplastic anemia; and (4) 6 with peripheral thrombocytopenia with/without neutropenia. Immunosuppressive treatment was associated with aminotransferases normalization in all but one child who required liver transplantation. Relapses occurred in 10 children. Lymphocytopenia was found at the time of the diagnosis of hepatitis in 13 children, 12 in groups 3 or 4. All 38 children are alive after 4-17 years, 18 still under immunosuppression. CONCLUSIONS: Childhood seronegative autoimmune hepatitis includes a spectrum of disorders. Early liver histology is recommended and, if compatible with autoimmune hepatitis, immunosuppressive treatment should be started. Initial lymphocytopenia may indicate future hematological complication.
Asunto(s)
Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/complicaciones , Hepatitis Autoinmune/terapia , gamma-Globinas/análisis , Adolescente , Anemia Aplásica/epidemiología , Autoanticuerpos/sangre , Niño , Preescolar , Femenino , Francia , Humanos , Inmunosupresores/uso terapéutico , Lactante , Italia , Hígado/patología , Fallo Hepático/epidemiología , Trasplante de Hígado , Masculino , Trombocitopenia/epidemiología , Transaminasas/sangreRESUMEN
The identification of drugs capable of reactivating γ-globin to ameliorate ß-thalassemia and Sickle Cell anemia is still a challenge, as available γ-globin inducers still have limited clinical indications. High-throughput screenings (HTS) aimed to identify new potentially therapeutic drugs require suitable first-step-screening methods combining the possibility to detect variation in the γ/ß globin ratio with the robustness of a cell line. We took advantage of a K562 cell line variant expressing ß-globin (ß-K562) to set up a new multiplexed high-content immunofluorescence assay for the quantification of γ- and ß-globin content at single-cell level. The assay was validated by using the known globin inducers hemin, hydroxyurea and butyric acid and further tested in a pilot screening that confirmed HDACs as targets for γ-globin induction (as proved by siRNA-mediated HDAC3 knockdown and by treatment with HDACs inhibitors entinostat and dacinostat) and identified Heme-oxygenases as novel candidate targets for γ-globin induction. Indeed, Heme-oxygenase2 siRNA knockdown as well as its inhibition by Tin protoporphyrin-IX (TinPPIX) greatly increased γ-globin expression. This result is particularly interesting as several metalloporphyrins have already been developed for clinical uses and could be tested (alone or in combination with other drugs) to improve pharmacological γ-globin reactivation for the treatment of ß-hemoglobinopathies.
Asunto(s)
Globinas beta/análisis , gamma-Globinas/análisis , Anemia de Células Falciformes/metabolismo , Ácido Butírico/metabolismo , Hemoglobina Fetal/metabolismo , Humanos , Hidroxiurea/metabolismo , Células K562 , Globinas beta/metabolismo , Talasemia beta/metabolismo , gamma-Globinas/metabolismoRESUMEN
Clinical severity assessment and molecular analysis of ß-, α-globin genes and the -158 (C > T) XmnI polymorphism of the (G)γ-globin gene were performed in 80 pediatric patients with Hb E (HBB: c.79G > A)/ß-thalassemia (ß-thal) to investigate the effects of coinheritance of α-thalassemia (α-thal) and other molecular determinants on their clinical severity. The mean age was 9.4 ± 5.1 years. By using clinical severity score, 35 (43.8%), 27 (33.8%) and 18 cases (22.5%) had moderate, mild and severe disease, respectively. Nine ß-thal mutations were identified. All were ß° or severe ß⺠mutations. Five patients (6.3%) had coinherited α°-thal. All five patients had mild disease with baseline hemoglobin (Hb) values of 7.9 ± 1.5 g/dL, mild hepatosplenomegaly and close-to-normal growth. Only one required a red blood cell transfusion. The disease severity was significantly different among the groups with and without α-thal (p = 0.025), but was not different among the groups with or without the XmnI polymorphism (p = 0.071). This study demonstrates that coinheritance of α°-thal alleviates the degree of disease severity in Hb E/ß-thal. All our patients with coinherited α°-thal have mild disease.
Asunto(s)
Hemoglobina E/genética , Mutación , Polimorfismo Genético , Globinas alfa/genética , Talasemia alfa/genética , Talasemia beta/genética , gamma-Globinas/genética , Adolescente , Niño , Preescolar , Codón , Desoxirribonucleasas de Localización Especificada Tipo II/metabolismo , Femenino , Estudios de Asociación Genética , Hemoglobina E/análisis , Hemoglobina E/metabolismo , Humanos , Lactante , Intrones , Masculino , Mutación Puntual , Polimorfismo de Longitud del Fragmento de Restricción , Estudios Retrospectivos , Eliminación de Secuencia , Índice de Severidad de la Enfermedad , Tailandia , Globinas alfa/análisis , Globinas alfa/metabolismo , Talasemia alfa/sangre , Talasemia alfa/complicaciones , Talasemia beta/sangre , Talasemia beta/complicaciones , Talasemia beta/fisiopatología , gamma-Globinas/análisis , gamma-Globinas/metabolismoRESUMEN
PURPOSE: The purpose of this study was to identify protein markers present in subjects with temporomandibular joint disorders (TMDs) and clicking compared with the levels in controls. MATERIALS AND METHODS: This was a pilot case-control study, and we report the preliminary results. Samples of joint aspirate collected from patients with TMDs and controls who had undergone surgery for a problem other than TMDs were analyzed using isobaric tags for relative and absolute quantitation (iTRAQ) and biotin-labeled-based protein arrays. The data obtained from these techniques were used to identify the proteins of interest, which were then quantitated using enzyme-linked immunosorbent assay (ELISA). The patient samples studied included joint aspirate collected clinically from the controls and patients and included samples from both the right and the left sides of each patient with a TMD. RESULTS: The 8 TMJ aspirate samples from 6 subjects included 5 aspirate samples from 4 patients and 3 from 2 controls. The greatest standardized protein concentration of endocrine gland-derived vascular endothelial growth factor/prokineticin-1 (EG-VEGF/PK1) and D6 was found in both joints of the controls compared with the levels from the joints of the patients. With 1 exception, the standardized protein concentration was significantly lower in the patients than in the controls. The lower levels of EG-VEGF/PK1 and D6 in the patients compared with the controls suggest that these cytokines might be possible biomarkers for TMDs. CONCLUSION: In the present pilot study, greater levels of EG-VEGF/PK1 and D6 were found in the controls than in the patients with TMDs. Proteomic analysis of the proteins present in the diseased joints compared with those in the controls might help to identify proteins present when pain or degeneration of the joint occurs. The proteomic information might be useful in the development of future therapies.
Asunto(s)
Biomarcadores/análisis , Proteoma/análisis , Trastornos de la Articulación Temporomandibular/diagnóstico , Activinas/análisis , Adolescente , Adulto , Anhidrasas Carbónicas/análisis , Estudios de Casos y Controles , Quimiocina CCL21/análisis , Femenino , Humanos , Factor II del Crecimiento Similar a la Insulina/análisis , Luxaciones Articulares/diagnóstico , Luxaciones Articulares/metabolismo , Metaloproteinasa 16 de la Matriz/análisis , Paracentesis , Peroxirredoxinas/análisis , Proyectos Piloto , Análisis por Matrices de Proteínas , Receptores CCR10/análisis , Líquido Sinovial/química , Disco de la Articulación Temporomandibular/patología , Trastornos de la Articulación Temporomandibular/metabolismo , Factor de Crecimiento Endotelial Vascular Derivado de Glándula Endocrina/análisis , Adulto Joven , Globinas alfa/análisis , Globinas beta/análisis , gamma-Globinas/análisis , Receptor de Quimiocina D6RESUMEN
Gammopathies associated with plasma cell neoplasms in a 15-year-old female spayed domestic shorthaired cat and a 9-year-old female spayed Rottweiler dog were evaluated by serum protein electrophoresis. In the cat, the plasma cell neoplasm was found in the liver and spleen, and an evaluable sample of bone marrow was not obtained. Some of the plasma cells had the morphologic appearance of flame cells. The paraprotein was confirmed as IgG based on agar gel immunodiffusion precipitation and both immunocytochemical and immunohistochemical staining. The dog had multiple myeloma with production of IgG and IgA paraproteins. In both cases, serum proteins were evaluated by 2 methods of protein electrophoresis: cellulose acetate electrophoresis (CAE) and capillary zone electrophoresis (CZE). In the cat and the dog, CAE showed a single large oligoclonal-like peak, which occurred in the γ-region in the cat and the ß-γ-region in the dog, whereas CZE showed a biclonal gammopathy with 2 very close narrow spikes in the γ- and ß-γ-regions in the cat and dog, respectively. In selected cases, CZE may be more effective than routine CAE in distinguishing oligoclonal from monoclonal or biclonal paraproteinemia.
Asunto(s)
Enfermedades de los Gatos/diagnóstico , Enfermedades de los Perros/diagnóstico , Electroforesis Capilar/veterinaria , Neoplasias de Células Plasmáticas/veterinaria , gamma-Globinas/análisis , Animales , Enfermedades de los Gatos/sangre , Enfermedades de los Gatos/patología , Gatos , Enfermedades de los Perros/sangre , Enfermedades de los Perros/patología , Perros , Electroforesis en Acetato de Celulosa/veterinaria , Femenino , Neoplasias de Células Plasmáticas/sangre , Neoplasias de Células Plasmáticas/diagnóstico , Neoplasias de Células Plasmáticas/patologíaRESUMEN
OBJECTIVE: To study the present situation of thalassemia among people at reproductive age in Guilin city. METHODS: A complete red blood cell mean cell volume (RBCMCV) was detected as well as hemoglobin electrophoresis analysis were done for all samples. Suspected alpha or beta thalassemia cases, were screened out and alpha and beta thalassemia genes were detected by PCR-RDB. RESULTS: Among 1580 cases, 79 cases were detected a thalassemia gene positive, with the detection rate as 5.00%. The detection rates on a thalassemia were 5.32%, 4.68% in males and females, but no significant difference (chi2 = 3.04, chi2 < chi0.05 (1) = 3.84, P > 0.05). 114 cases were detected carrying beta thalassemia gene with the detection rate as 7.22%. The detection rates on beta thalassemia were 7.85%, 6.58% in males and females, with no significant difference (chi2 = 0.95, chi2 < chi0.05(l) = 3.84, P > 0.05). The overall detection rate of thalassemia was 12.22% (193/1580). Alpha thalassemia were found to have had ten genotypes, with --SEA/alphaalpha the most common one and the detection rate was 3.54%. -Alpha(3.7)/alphaalpha appeared the majority in the static alpha thalassemia and --SEA/alphaalpha took the majority in the light a thalassemia, while --SEA-alphaCS was the major one in the intermedia alpha thalassemia, with gene contributions of 7.59%, 70.88% and 2.53%. Beta thalassemia was detected having seven genotypes,with CD41-42 (-TTCT) the most common one in beta thalassemia, and the detection rate was 3.16%. The commonly seen three mutations, CD41-42 (-TTCT), CD17 (A-->T) and IVS-II-654 (C-->T) were accounted for 87.71% of beta thalassemia. The detection rate on thalassemia a and beta combination was 0.63%. CONCLUSION: The detection rate of thalassemia among people at productive age in Guilin city was relatively high.
Asunto(s)
Talasemia alfa/epidemiología , Talasemia beta/epidemiología , Adulto , China/epidemiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Talasemia alfa/genética , Talasemia beta/genética , gamma-Globinas/análisisRESUMEN
The genesis of auto-immune antibodies directed against the own tissue antigens of a host may be due to the host's immune response to mycobacteria. The prospective study included 110 patients treated for active pulmonary tuberculosis and the control group of 60 healthy subjects, volontary blood donors. Applying the method of indirect immnunofluorescence and cryostat sections of rat organs and human larynx cancer epithelial cell line (HEp-2 cells), the prescence of the following autoantibodies in the serum of the examined patients was examined: anti,nclear (ANA), anticardiac (ACA), antimitochondrial (AMA), antiparietal (APA), anti smooth muscular (ASMA), antithyroidal (ATA), rheumnatoid factor (RF). These autoantibodies were determined in the course oftreatment and five years later. Low levels of some examined autoantibodies were detected in the serum of a number of the examined patients. No significant difference in the presence of the analysed antibodies was registered between the sexes. In the course of the treatment a reversible hyper-gammaglobulinemia developed, which was at least partially due to the presence of autoantibodies in the patients blood serum. Besides possibly involved mechanisms of molecular mimicry and polyclonal lymphocyte activation, the presence of antinuclear antibodies in the patient's serum is at least partially due to isoniazide treatment. The finding of other autoantibodies is nonspecific and not related to the mycobacterial infection or antituberculosis drug administration.