Association between HLA-DQ alleles and Leprosy in Indonesia Javanese population

ABSTRAK Penelitian sebelumnya menunjukkan bahwa kerentanan terhadap penyakit lepra dan respon antibodi anti M. /eprae pada populasi Jawa berhubungan dengan faktor genetik HLA-DR. Untuk mengetahui apakah kerentanan tersebut juga berhubungan dengan HLA-D0, telah dilakukan penelitian lanjutan dengan memeriksa fenotipfenotip HLA-DQ dan pemeriksaan antibodi terhadap 79 penderita lepra (terdiri atas 41 lepra TT/BT dan 38 lepra LL/BL) dan 50 kontrol sehat dari populasi yang sama.\u27 Penggolongan HLA-DQ dilakukan dengan metode SSO (sequence specific oligonucleotide typing), sedangkan pemeriksaan antibodi dilakukan dengan tes ELISA dan ELISA-INHIBISI. Hasil penelitian menunjukkan adanya hubungan antara HLA-DQB501 dengan lepra, baik TT maupun LL (OR: 3,2795% CI 1,42-7,60). Jika HLA-DQ1 secara keseluruhan dianalisis, hubungan bermakna hanya dijumpai terhadap lepra lepromatosa (OR:9,1895% CI 1,89-86,30). Antibodi IgG anti protein 36 kD ternyata berhubungan dengan HLA-DQA1O2. Titer IgG anti 36 kD dijumpai Iebih tinggi pada HLA-DQA1O2 positif dibandingkan HLA-DQA1O2 negatif. Tidak ada hubungan antara HLA-DQ dengan seropositivitas balk IgM maupun IgG anti M. /eprae (p>0,05). Disimpulkan bahwa selain HLA-DR, ternyata kerentanan terhadap lepra pada populasi ini diatur juga oleh gen pada lokus HLA-DQ. Penelitian ini juga menyokong penelitian-penelitian lain sebelumnya bahwa HLA-DQ1 merupakan penanda universal kerentanan terhadap lepra lepromatosasedangkan infeksi subklinis M. /eprae tidak diatur oleh faktor genetik HLA. Key words : leprosy â M. leprae â genetic factors â HLA-DQ â HLA-DQ1 â HLA-DQB5O

Multi Drug Therapy (MDT). Lepra

ABSTRAK Effective chemotherapy is an important aspect in leprosy control, which may interrupt the chain of transmission of the disease in the community and avoid permanent disabilities. The use of dapsone monotherapy in leprosy has given rise to the problems of dapsone resistance, persistence of M. leprae and drug uncompliance. Multi Drug Therapy (MDT) has been recommended to overcome the problems. The mechanism of action and regimens of MDT, prerequisites and evaluation of the implementation of MDT have been discussed. Key Words: MDT, Dapsone, Clofasimine, Ftifampicin, paucibacillary leprosy, multibacillary lepros

Reaktivitas sel-T dan sel-B penderita lepra dan narakontak terhadap beberapa antigen atau epitop Mycobacterium leprae

This study was aimed at evaluating the T cell and B cell reactivity against Mycobacterium Ieprae antigens or epitopes among leprosy patients and their household contacts in the Indonesian population. Through this study, M. Ieprae epitopes (either protective or suppresive) will be identified and hopefully proved useful for the development of an effective leprosy vaccine in the future. Fifty-nine leprosy patients consisting of 34 tuberculoid type (TT/BT) and 24 lepromatous type (LUBL) at Dr. Sardjito General Hospital Yogyakarta and 50 household contacts were recruited for this study. After the informed consent was given, 20 ml venous blood was drawn from each subject for assays of the T cell and B cell reactivities. The T cell reactivity was tested by lymphocyte transformation (LTT) and the B cell reactivity was tested serologically by EUSA. M. leprae antigen, PGL-I and some recombinant proteins (65 kD, 30 kD, 45 kD and 43 kD) were used as antigens in both assays. In addition, Phytohemagglutinin (PHA) and Interleukin-2 (IL-2) were used as mitogens in the LTT. Statistical analysis was done by using One way ANOVA and Chi-square tests. The results showed that cellular immune deficiency in LUBL patients was found to be specific to the M. leprae antigen, but not to mitogens and other antigens. The T-lymphocyte of the patients (either TT/BT or LUBL) and healthy contacts demonstrated very low reactivities againts all recombinant antigens. On the other hand, the sera of LUBL leprosy patients reacted significantly against all antigens, most strikingly against PGL-I and 43 recombinant protein of M. leprae. Whereas, the sera of TT/BT patients and healthy contacts showed no or least reactivity against those antigens. These data indicate that although in a small proportion M. leprae recombinant proteins of 65 kD, 30 kD, 45 kD and 43 kD are recognized by T-cell of leprosy patients and healthy contacts. These antigens contain more B-cell epitopes rather than T-cell epitopes. So, these antigens should be eliminated as soon as a possible candidate in the development of any leprosy vaccine. Key words: leprosy - T-cell and B-cell - Mycobacterium leprae antigen ELISA - tuberculoid and lepromatouse type

Pengembangan vaksin lepra

ABSTRAK The problems of current approach to leprosy control through case detection and mass treatment are well understood. Therefore, a primary prevention strategy through vaccination would appear to be the answer. Efforts are now being made to develop avaccine which is highly effective and efficient BCG, a vaccine first used for tuberculosis, has proved to have a protective effect against leprosy. Some studies in human subjects have shown that preparation of killed M. leprae and BCG can induce cell-mediated immunity in lepromin negative patients and healthy contacts. Large field trials in different population are now underway. The progress in the field of basic immunology and molecular biology has given impetus to search for a more specific vaccine for leprosy. Use of recombinant DNA technology permit mass production of M. leprae antigens at low cost. Studies of these antigens are now still performed in the T cell levels to identify their protective epitopes. In addition, a carrier system for vaccine that should be effective, acceptable and cheap, is also being investigated. Key Words : leprosy vaccine, BCG, killed M. leprae antigens, recombinant antigens, protective epitope

Antibodi monoklonal terhadap antigen protein 36 kd dari Mycobacterium leprae dan aplikasinya dalam serodiagnosis lepra

ABSTRAk Identification of M. leprae antigens and development of monoclonal antibodies CO those antigens have brought about progress in the serodiagnosis of leprosy and have partly overcome the limitations of clinical, bacteriological dan histopathological diagnosis. Thirty six kD protein antigen of M. leprae contains a specific epitope of M. leprae which is recognized both by monoclonal antibody and by T-cells. Elisa Inhibition is a serological test using the monoclonal antibody to the 36 kD protein of M. leprae antigen. In Indonesian populations, this test shows high sensitivity (98.1% for multibacilaty and 81.8% for paucibacilary leprosy) with 92% specificity. Compared to the ocher serological tests, using monoclonal antibody in the test has resulted in higher sensitivity and specificity. Because of the high sensitivity for both paucibacilary and multibaciltary leprosy, it is suggested that the.epiu3p on 36 kI) protein of M. leprae antigen is immunodominant. This paper describes preparation of antigen and monoclonal antibody, and the Elisa Inhibition test, and application in serodiagnosis of leprosy and infection ofM leprae. Key Words : leprosy, M. leprae, 36 kD protein. antigen, monoclonal antibody, epitope, immunodominant, Elisa Inhibition assay

Association between atopy and allergic contact dermatitis in Dr. Sardjito General Hospital Yogyakarta

Association between atopy and development of allergic contact dermatitis (ACD) remains controversial. T cell disfunctions in a patient with atopy complicate the process of nickel sensitization. On the other, the decrease of the skin barrier function and overexpression of Langerhans cells in the patient facilitate the sensitization.  This study aimed to evaluate the association between atopy and incidence of nickel ACD. A case-control study was carried out in Allergic and Immunology Sub Department of Dermato-Venereology Policlinic, Dr. Sardjito General Hospital, Yogyakarta, involving 54 nickel ACD patients as case group and 74 healthy subjects as control group. All subjects underwent prick test allergens i.e. house dust, dust mite, cockroach, mixed fungi, nuts and egg white. The skin reaction was considered as a positive result if a wheal diameter of at least 3 mm larger than the negative control or a minimum of half of the positive control. The relationship between atopy and the nickel ACD incidence was analyzed using Chi-Square test with confidence interval (CI) of 95%. A significant association between atopy and the nickel ACD incidence was observed in this study. Subjects with atopy to  ≥1 allergen had risk of nickel ACD 3.74 higher than subjects without atopy (odds ratio/OR=3.74; 95%CI = 1.64-8.53).  Furtheremore, subjects with atopy to  ≥2 allergens had risk of nickel ACD 3.74 higher than subjects without atopy (OR=2.08; 95%CI = 1.01-4.29). In conclusion, atopy is a risk factor of nickel ACD

Immunopathogenesis of severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) infection: a concise update

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus which has been identified as the cause of the recently emerging coronavirus disease 2019 (COVID-19), a respiratory-related infectious disease, in late 2019. As of May 2020, SARS-CoV-2 has infected millions of people with almost 300.000 deaths worldwide only within few months since its first case was reported. While this infection mostly results in mild diseases, the increasing number of severe cases and deaths cannot be overlooked. Due to its novelty, many facets of SARS-CoV-2 pathogenesis are not well understood. This review presents updated knowledge on the key virus characteristics of SARS-CoV-2 and critical notes in the pathogenesis of this viral infection in human that is currently proposed to largely involve various aspects of the host immune responses. While the immediate impact of viral infection in the target cells contributes to the development of the disease, the ability of the virus to modify the host responses may result in the dysregulation of innate and adaptive immune responses, which commonly manifest in the severe spectrum of the disease. Having deep understanding on this complex process is central for tailoring appropriate management for the infected patients as well as for developing effective preventive measures, most importantly vaccine, which is hoped to occur in the near future

Systematic review: better or (otherwise) misleading for clinical decision?

Systematic review is a method to combine multiple sources of evidence through an explicit and reproducible way ofliterature search and critical appraisal of the quality of included studies, with or without mathematical methods tosynthesis these information. Since this method was first introduced more than centuries ago, systematic review hasbeen increasingly popular and widely used particularly in the area of medicine. Systematic review is often veryuseful to physicians to help supporting the clinical decision making and significantly reducing their time to seek forappropriate evidence. However, despite its reproducible and systematic steps to substantially minimize the presenceof biases, physicians should still be aware that systematic review is not completely biases resistant. Inclusion ofpoor quality studies, heterogeneity, and publication or other reporting biases are commonly evident in systematicreview that may hinder the quality of the conclusion. This review summarizes the core principals of systematicreview and its potential biases, and discusses when the systematic review is useful or needing careful attention.Key words: treatment-scientific evidence- meta-analysis- critical appraisal-outcome

Potential skin problems of diabetes mellitus patients: a review

Diabetes mellitus (DM) is one of the common metabolic disorders, and a major part of chronic diseases, the prevalence of which tends to increase due to multifactor. Blood vessels, kidneys, lungs, and skin are among the organs that are affected. The first problem that arises, or commonly exists among one-third of diabetics, are problems with their skin, although skin lesions may develop along with the progress of the disease, or can occur during the later phase of DM. The prevalence and symptoms of skin problems in type 1 DM (T1DM) and type 2 DM (T2DM) are often unclear, and at the beginning of the course of the diseases they often go undiagnosed. Several theories regarding the pathophysiology of DM can be used as a logical reference for the early identification and diagnosis of skin problems, aimed at preventing the worsened condition. The use of skin autofluorescence (SAF) and AGEs reader in several cases of skin problems, can also be an important marker as an adjunct to predict the possibility and progressiveness of DM. Skin problems linked to patients with DM can be categorized as strongly related to diabetes, non-specific and related to DM, skin infection in DM, and skin problems due to diabetic medication. With the current COVID-19 pandemic, there are additional demands for more critical investigation of skin problems in patients with DM. The skin problems that occur in DM may need to be examined from the early stage and it is necessary to inhibit the progression of skin problems, as well as to consider the need for multidisciplinary DM therapy

Association between environmental allergen sensitization with severity of atopic dermatitis in children and young adult at Dr. Sardjito General Hospital, Yogyakarta

The important role of aeroallergens and food allergens as the most common environmental allergens in exacerbationof atopic dermatitis (AD) iswell known. Sensitization is an essential processwhich correlateswith clinicalmanifestationof AD. The study of AD in Indonesia, especially in Yogyakarta, has not been reported, yet. The aim of study is toevaluate the association between sensitization of environmental allergens with clinical severity of AD in children andyoung adult at Dr. Sardjito General Hospital, Yogyakarta. An analytic observational cross sectional study wasperformed on 33 children and young adult with AD. The severity of disease was determined by SCORing AtopicDermatitis (SCORAD). Assessment of sensitization was performed using specific IgE serum, atopy patch test, andprick test. Data were analyzed using chi-square or Fisher exact test and prevalence ratio (PR) with significancevalue of p<0.05 and 95%confidence interval (CI). The results showed that specific IgE positivity was associatedwith severity of AD. Percentage of specific IgE positivity to house dust mite was significantly higher in subject withmoderate/severe AD compared to those of mild AD (p=0.049; PR 1.13; 95% CI 1.01-1.59). The result was alsosimilar for cat dander (p=0.041; PR 1.1; 95%CI 1.09-4.98), cow’s milk (p=0.038; PR 1.21; 95% CI 1.02-2.2),and egg white (p=0.027; PR 1.23; 95% CI 1.15-2.97). Whereas specific IgE positivity to fish allergen was notstatistically different in subject with moderate/severe AD compared to those with mild AD (p=0.061; PR 0.8; 95%CI 0.76-2.8). According to atopy patch test and prick test result, no association was found between allergensensitization and severity of AD. If allmethodswere combined to increase the sensitivity of sensitizationmeasurement,then the association was found for all allergens. It could be concluded that environmental allergens sensitization isassociated with severity of AD in children and young adult at Dr. Sardjito General Hospital, Yogyakarta.Key words: atopic dermatitis-disease severity-sensitization-aeroallergen-food allerge