Imunofenotipagem de linfócitos e macrófagos de lesões de pele de pacientes com diferentes formas de hanseníase segundo a classificação de Ridley e Jopling

Abstract

Introduction: There are different leprosy classification methods. World Health Organizations operational classification differentiates patients in paucibacillary (with up to five skin lesions) and multibacillary (six or more lesions). This classification is recommended by the Ministry of Health of Brazil and facilitates the choice of the drug regimen to be used. The Ridley and Jopling classification differentiates patients according to their clinical, histopathological, bacteriological and immunological presentation and is the most widely used scientific classification. Despite the undeniable practicality, different authors have pointed out flaws in the operational classification, compared to Ridley and Jopling classification, especially discrepancies regarding the differentiation of patients with paucibacillary and multibacillary leprosy. Many patients considered multibacillary by Ridley and Jopling classification are erroneously classified as paucibacillary by the operational classification. This mistake may result in inadequate treatment duration, underestimation of the sequelae risk associated with the disease and difficulty for the epidemiological control of leprosy, since it is especially underpinned in the early and proper treatment of patients. On the other hand, different authors have shown that the Ridley and Jopling classification, though more complete, presents considerable disagreement among its clinical and histological components. Objective: This study aimed to compare different leprosy classification methods and evaluate lymphocytes and macrophages immunohistochemistry in biopsies of different forms of leprosy. It was designed considering that the histopathological approach with in situ immunophenotyping of inflammatory cells in the lesions can bring advances in the understanding of the rational grounds of leprosy classification. Methods: The study included patients with newly diagnosed leprosy seen at the Eduardo de Menezes Hospital (Hospital Foundation of Minas Gerais State). Patients underwent skin biopsy and the material was processed in the Neuroimmunopathology laboratory of UFMG Institute of Biological Sciences for HE, Wade, Prussian blue and immunohistochemistry (CD3, CD4, CD8, CD62L, CD68, CD14, CD16, CD163, L1) staining. Results: 53 patients were included, with different forms of leprosy. The agreement between the operational classification and the classification used in the reference service (Ridley and Jopling classification plus the recommendation that the skin slit smear positivity, even alone, categorizes the patient as multibacillary) was moderate (kappa = 0.49). The operational classification overestimated the number of MB patients (42.9% vs. 38.8%) and classified as paucibacillary 26.3% of patients considered multibacillary the reference service classification. The full concordance between the clinical and pathological components of the Ridley and Jopling classification occurred in only 46.9% of cases. In the immunohistochemical study, the ratio of CD4+/CD8+ cells was more consistent with the classic paradigm Th1xTh2 than the CD3, CD4 or CD8 markings alone. The CD163 positivity represented better the phenotypic variation of macrophages involved in the inflammatory process of different forms of leprosy than the markings for CD68, CD62L, CD14, CD16, L1 and iron. Conclusions: The operational classification overestimates the number of MB patients, and it has a high rate of "false-paucibacillary" patients. The disagreement between the clinical and histopathological components of Ridley and Jopling classification generally does not change the patient bacillary state (pauci / multi) and appears to result from an inaccuracy of the pathological criteria of the key used for histopathological classification. M2 CD163+ macrophages presented the better relationship with the Th1xTh2 paradigm in the lesions of different forms of leprosy, but its quantification, alone, does not detail the patients enough in order to add objectivity to the histopathological criteria of the Ridley and Jopling classification.