多菌型麻风病患者中PHEX的下调：观察性横断面研究

Downregulation of PHEX in multibacillary leprosy patients: observational cross-sectional study.

作者信息

Silva Sandra R Boiça, Illarramendi Ximena, Tempone Antonio J, Silva Pedro H L, Nery José A C, Monteiro Alexandra M V, Pessolani Maria Cristina V, Boasquevisque Edson, Sarno Euzenir N, Pereira Geraldo M B, Esquenazi Danuza

机构信息

Disciplina de Patologia Geral e Laboratório de Imunopatologia, Departamento de Patologia e Laboratórios, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro (UERJ), Av Professor Manuel de Abreu 444, Vila Isabel, Rio de Janeiro, RJ, 20550-170, Brazil.

Laboratório de Hanseníase, Instituto Oswaldo Cruz (IOC) - Oswaldo Cruz Foundation (FIOCRUZ), Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ, 21040-360, Brazil.

出版信息

J Transl Med. 2015 Sep 11;13:296. doi: 10.1186/s12967-015-0651-5.

DOI:10.1186/s12967-015-0651-5

PMID:26362198

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4566286/

Abstract

BACKGROUND

Peripheral nerve injury and bone lesions, well known leprosy complications, lead to deformities and incapacities. The phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) encodes a homonymous protein (PHEX) implicated in bone metabolism. PHEX/PHEX alterations may result in bone and cartilage lesions. PHEX expression is downregulated by intracellular Mycobacterium leprae (M. leprae) in cultures of human Schwann cells and osteoblasts. M. leprae in vivo effect on PHEX/PHEX is not known.

METHODS

Cross-sectional observational study of 36 leprosy patients (22 lepromatous and 14 borderline-tuberculoid) and 20 healthy volunteers (HV). The following tests were performed: PHEX flow cytometric analysis on blood mononuclear cells, cytokine production in culture supernatant, 25-hydroxyvitamin D (OHvitD) serum levels and (99m)Tc-MDP three-phase bone scintigraphy, radiography of upper and lower extremities and blood and urine biochemistry.

RESULTS

Significantly lower PHEX expression levels were observed in lepromatous patients than in the other groups (χ(2) = 16.554, p < 0.001 for lymphocytes and χ(2) = 13.933, p = 0.001 for monocytes). Low levels of 25-(OHvitD) were observed in HV (median = 23.0 ng/mL) and BT patients (median = 27.5 ng/mL) and normal serum levels were found in LL patients (median = 38.6 ng/mL). Inflammatory cytokines, such as TNF, a PHEX transcription repressor, were lower after stimulation with M. leprae in peripheral blood mononuclear cells from lepromatous in comparison to BT patients and HV (χ(2) = 10.820, p < 0.001).

CONCLUSION

Downregulation of PHEX may constitute an important early component of bone loss and joint damage in leprosy. The present results suggest a direct effect produced by M. leprae on the osteoarticular system that may use this mechanism.

摘要

背景

周围神经损伤和骨病变是众所周知的麻风并发症，可导致畸形和残疾。与X染色体上的内肽酶具有同源性的磷酸盐调节基因（PHEX）编码一种与骨代谢有关的同名蛋白（PHEX）。PHEX/PHEX改变可能导致骨和软骨病变。在人雪旺细胞和成骨细胞培养物中，细胞内麻风分枝杆菌（M. leprae）可下调PHEX表达。M. leprae在体内对PHEX/PHEX的影响尚不清楚。

方法

对36例麻风患者（22例瘤型和14例界线类偏结核型）和20名健康志愿者（HV）进行横断面观察研究。进行了以下检查：对血液单核细胞进行PHEX流式细胞术分析、培养上清液中的细胞因子产生、25-羟基维生素D（OHvitD）血清水平和（99m）Tc-MDP三相骨闪烁显像、上下肢X线摄影以及血液和尿液生化检查。

结果

瘤型患者的PHEX表达水平明显低于其他组（淋巴细胞：χ(2)=16.554，p<0.001；单核细胞：χ(2)=13.933，p=0.001）。健康志愿者（中位数=23.0 ng/mL）和界线类偏结核型患者（中位数=27.5 ng/mL）的25-(OHvitD)水平较低，瘤型患者血清水平正常（中位数=38.6 ng/mL）。与界线类偏结核型患者和健康志愿者相比，瘤型患者外周血单核细胞经麻风分枝杆菌刺激后，肿瘤坏死因子（TNF，一种PHEX转录抑制因子）等炎性细胞因子水平较低（χ(2)=10.820，p<0.001）。