Assuntos
Apoptose/efeitos dos fármacos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/uso terapêutico , Linhagem Celular Tumoral , Humanos , Prognóstico , Transdução de Sinais/efeitos dos fármacosRESUMO
Chronic lymphocytic leukemia (CLL) is a malignant disorder of B cell origin, with low incidence in Asian populations. In this study we investigated the HLA-class I A and B allele frequencies in 87 Iranian CLL patients and 64 healthy controls using sequence specific primer-polymerase chain reaction (SSP-PCR) technique. Our results showed increased frequencies of HLA-A11:01 (p=0.02) and HLA-B35:01 (p=0.002) alleles and HLA-A11:01/B35:01 haplotype (p=0.036) and decreased frequencies of HLA-A01:01 (p=0.02), HLA-A26:01 (p=0.03), HLA-B65:01 (p=0.03) and HLA-B53:01 (p<0.00001) alleles in CLL patients compared to the control group. Classification of the patients into non-progressive and progressive groups did not reveal significant differences for the frequency of any of the HLA-A and -B alleles or haplotypes between these two subtypes. Comparison between patients with immunoglobulin heavy chain variable region genes (IGHV) mutated (n=56) and unmutated (n=31) subtypes showed a significant increase in HLA-A32:01 (p=0.05) and HLA-A33:01 (p=0.05) alleles in IGHV unmutated patients compared to IGHV mutated patients. Similarly, a higher frequency of HLA-B52:01 (p=0.037) alleles was observed in CD38(+) compared with CD38(-) patients. Our results obtained from an Iranian population indicate that CLL is associated with distinct HLA class I alleles and haplotypes some of which are linked to disease prognostic factors.
Assuntos
Linfócitos B/imunologia , Etnicidade , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Leucemia Linfocítica Crônica de Células B/imunologia , ADP-Ribosil Ciclase 1/metabolismo , Adulto , Progressão da Doença , Feminino , Frequência do Gene , Genótipo , Haplótipos , Teste de Histocompatibilidade , Humanos , Irã (Geográfico) , Leucemia Linfocítica Crônica de Células B/genética , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
ROR1 is a receptor tyrosine kinase (RTK) recently identified to be overexpressed at the gene and protein levels in chronic lymphocytic leukemia (CLL). Monoclonal antibodies (MAbs) against RTKs have been successfully applied for therapy of solid tumors. We generated five MAbs against the Ig (n = 1), cysteine-rich (CRD) (n = 2) and kringle (KNG) (n = 2) domains, respectively, of the extracellular part of ROR1. All CLL patients (n = 20) expressed ROR1 on the surface of the leukemic cells. A significantly higher frequency of ROR1 expression was found in patients with progressive versus non-progressive disease, and in those with unmutated versus mutated IgVH genes. All five MAbs alone induced apoptosis in the absence of complement or added effector cells (Annexin-V and MTT, as well as cleavage of poly-(ADP ribose)-polymerase, caspase-8 and caspase-9) of CLL cells but not of normal B cells. Most effective were MAbs against CRD and KNG, significantly superior to rituximab (P < 0.005). Cross-linking of anti-ROR1 MAbs using the F(ab')(2) fragments of anti-Fc antibodies significantly augmented apoptosis. Two of the MAbs induced complement-dependent cytotoxicity (CDC) similar to that of rituximab and one anti-ROR1 MAb (KNG) (IgG1) showed killing activity by antibody-dependent cellular cytotoxicity. The identified ROR1 epitopes may provide a basis for generating human ROR1 MAbs for therapy.
Assuntos
Anticorpos Monoclonais/farmacologia , Apoptose/imunologia , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/patologia , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/imunologia , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Animais , Formação de Anticorpos , Citotoxicidade Celular Dependente de Anticorpos , Humanos , Imunização , Leucemia Linfocítica Crônica de Células B/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fragmentos de Peptídeos/imunologia , Células Tumorais CultivadasRESUMO
BACKGROUND: Vitiligo is an acquired idiopathic hypomelanotic disorder characterized by circumscribed depigmented macules resulting from the loss of cutaneous melanocytes. OBJECTIVE: In order to evaluate the immune system of Iranian patients with vitiligo, this study was accomplished. METHODS: Fifty-five Iranian patients with vitiligo and 60 healthy persons as control were investigated in this study. The laboratory techniques were included: antimelanocyte antibody (AMA) and antinuclear antibody (ANA) with indirect immunoflorescent test, C3 and C4 levels with single radial immunodiffusion (SRID), and rheumatoid factor (RF) with enzyme-linked immunosorbent assay (ELISA). RESULTS: AMA was positive in 17 patients (30.9%) and was negative in the entire control group (P < 0.0001). ANA was positive in 4 patients (7.3%), which was insignificantly higher than control group (1.7%). IgM-RF was positive in 6 patients (10.8%) while it was negative in the entire control group (P = 0.027). C3 and C4 values decreased in 14 patients (25.5%), which was significantly higher than control group (P < 0.001). CONCLUSION: The important role of the immune system in the pathogenesis of vitiligo could be suggested. In addition, the autoimmune hypothesis of vitiligo could be confirmed based on the results of this study.
