ANALISIS PERAN DEWAN PENGAWAS SYARIAH DALAM MENINGKATKAN KUALITAS KINERJA OPERASIONAL DI BMT SABILIL MUTTAQIEN GISTING TANGGAMUS

ABSTRAK Dewan pengawas syariah atau yang biasa disingkat dengan DPS merupakan suatu badan/independen yang ditempatkan oleh dewan syariah nasional pada lembaga keuangan syariah. Anggota DPS harus terdiri dari para pakar dibidang syariah muamalah yang memiliki pengetahuan umum dibidang perbankan. Tugas Dewan Pengawas Syariah adalah memberikan nasihat dan saran kepada direksi serta mengawasi kegiatan lembaga keuangan syariah (LKS) agar sesuai dengan prinsip syariah. Tujuan dari penelitian ini adalah untuk mengetahui tugas dewan pengawas syariah di BMT Sabilil Muttaqien Gisting, Tanggamus dan untuk mengetahui bagaimana peran Dewan Pengawas Syariah dalam meningkatkan kualitas kinerja operasional di BMT Sabilil Muttaqin Gisting, Tanggamus. Penelitian ini bersifat penelitian kualitatif deskriftif, dimana pengumpulan datanya menggunakan metode observasi, wawancaradan dokumentasi. Teknik analisis data menggunakan data reduction(reduksi data), data display (peyajian data) dan conclusion drawing (verifikasi) dengan menggunakan triangulasi teknik. Sebelum menganalisis data, data yang ada dikelompokkan berdasarkan jenisnya masing-masing kemudian dianalisa dengan menggunakan suatu metode untuk memaparkan dan menafsirkan data yang ada. Setelah data dianalisa, kemudian peneliti mengambil kesimpulan-kesimpulan dengan berfikir induktif yaitu berangkat dari kesimpulan-kesimpulan khusus kemudian ditarik menjadi semua kesimpulan umum. Hasil dari penelitian ini ditemukan bahwa: pertama, tugas Dewan Pengawas Syariah di BMT Sabilil Muttaqien Gisting Tanggamus sudah terlaksana dengan baik. Hal tersebut bias dilihat dari tugas yang seharusnya dilakukan oleh dewan pengawas syariah: menilai dan memastikan pemenuhan prinsip syariah atas pedoman operasional dan produk yang di keluarkan bank; mengawasi proses perkembangan produk baru bank agar sesuai dengan fatwa DPS-DSN; meminta fatwa kepada DSN-MUI untuk produk baru bank yang belum ada fatwanya; melakukan review secara berkala atas pemenuhan prinsip syariah terhadap mekanisme penghimpunan dana dan penyaluran dana serta pelayanan jasa bank; dan meminta data dan informasi terkait aspek syariah dari satuan kerja bank dalam rangka pelaksanaan tugasnya. Kedua, dewan pengawas syariah di BMT Sabilil Muttaqien gisting memiliki peran penting dalam meningkatkan kinerja operasional, akan tetapi peran tersebut belum optimal. Hal tersebut terjadi karena DPS yang seharusnya secara rutin dan aktif melakukan pengawasan terhadap BMT Sabilil Muttaqien akan tetapi pengawasan tersebut hanya dilakukan ketika BMT tersebut memiliki masalah

Granzyme A Required for Regulatory T-Cell Mediated Prevention of Gastrointestinal Graft-versus-Host Disease

In our previous work we could identify defects in human regulatory T cells (Tregs) likely favoring the development of graft-versus-host disease (GvHD) following allogeneic stem cell transplantation (SCT). Treg transcriptome analyses comparing GvHD and immune tolerant patients uncovered regulated gene transcripts highly relevant for Treg cell function. Moreover, granzyme A (GZMA) also showed a significant lower expression at the protein level in Tregs of GvHD patients. GZMA induces cytolysis in a perforin-dependent, FAS- FASL independent manner and represents a cell-contact dependent mechanism for Tregs to control immune responses. We therefore analyzed the functional role of GZMA in a murine standard model for GvHD. For this purpose, adoptively transferred CD4+CD25+ Tregs from gzmA-/- mice were analyzed in comparison to their wild type counterparts for their capability to prevent murine GvHD. GzmA-/- Tregs home efficiently to secondary lymphoid organs and do not show phenotypic alterations with respect to activation and migration properties to inflammatory sites. Whereas gzmA-/- Tregs are highly suppressive in vitro, Tregs require GZMA to rescue hosts from murine GvHD, especially regarding gastrointestinal target organ damage. We herewith identify GZMA as critical effector molecule of human Treg function for gastrointestinal immune response in an experimental GvHD model

Alpha-1 Antitrypsin Augmentation Inhibits Proteolysis of Neutrophil Membrane Voltage-Gated Proton Channel-1 in Alpha-1 Deficient Individuals

Background and Objectives: Alpha-1 antitrypsin is a serine protease inhibitor that demonstrates an array of immunomodulatory functions. Individuals with the genetic condition of alpha-1 antitrypsin deficiency (AATD) are at increased risk of early onset emphysematous lung disease. This lung disease is partly driven by neutrophil mediated lung destruction in an environment of low AAT. As peripheral neutrophil hyper-responsiveness in AATD leads to excessive degranulation and increased migration to the airways, we examined the expression of the membrane voltage-gated proton channel-1 (HVCN1), which is integrally linked to neutrophil function. The objectives of this study were to evaluate altered HVCN1 in AATD neutrophils, serine protease-dependent degradation of HVCN1, and to investigate the ability of serum AAT to control HVCN1 expression. Materials and Methods: Circulating neutrophils were purified from AATD patients (n = 20), AATD patients receiving AAT augmentation therapy (n = 3) and healthy controls (n = 20). HVCN1 neutrophil expression was assessed by flow cytometry and Western blot analysis. Neutrophil membrane bound elastase was measured by fluorescence resonance energy transfer. Results: In this study we demonstrated that HVCN1 protein is under-expressed in AATD neutrophils (p = 0.02), suggesting a link between reduced HVCN1 expression and AAT deficiency. We have demonstrated that HVCN1 undergoes significant proteolytic degradation in activated neutrophils (p < 0.0001), primarily due to neutrophil elastase activity (p = 0.0004). In addition, the treatment of AATD individuals with AAT augmentation therapy increased neutrophil plasma membrane HVCN1 expression (p = 0.01). Conclusions: Our results demonstrate reduced levels of HVCN1 in peripheral blood neutrophils that may influence the neutrophil-dominated immune response in the AATD airways and highlights the role of antiprotease treatment and specifically AAT augmentation therapy in protecting neutrophil membrane expression of HVCN1

Granzyme A Is Required for Regulatory T-Cell Mediated Prevention of Gastrointestinal Graft-versus-Host Disease

<div><p>In our previous work we could identify defects in human regulatory T cells (Tregs) likely favoring the development of graft-versus-host disease (GvHD) following allogeneic stem cell transplantation (SCT). Treg transcriptome analyses comparing GvHD and immune tolerant patients uncovered regulated gene transcripts highly relevant for Treg cell function. Moreover, granzyme A (GZMA) also showed a significant lower expression at the protein level in Tregs of GvHD patients. GZMA induces cytolysis in a perforin-dependent, FAS-FASL independent manner and represents a cell-contact dependent mechanism for Tregs to control immune responses. We therefore analyzed the functional role of GZMA in a murine standard model for GvHD. For this purpose, adoptively transferred CD4⁺CD25⁺ Tregs from <i>gzmA</i>^-/- mice were analyzed in comparison to their wild type counterparts for their capability to prevent murine GvHD. <i>GzmA</i>^-/- Tregs home efficiently to secondary lymphoid organs and do not show phenotypic alterations with respect to activation and migration properties to inflammatory sites. Whereas <i>gzmA</i>^-/- Tregs are highly suppressive <i>in vitro</i>, Tregs require GZMA to rescue hosts from murine GvHD, especially regarding gastrointestinal target organ damage. We herewith identify GZMA as critical effector molecule of human Treg function for gastrointestinal immune response in an experimental GvHD model.</p></div

<i>GzmA</i>^<i>-/-</i> Tregs are required for prevention of gastrointestinal GvHD.

<p>Lethally irradiated BALB/c mice (n = 9) received T cell depleted (TCD) bone marrow cells (BM) together with CD4⁺CD25^- T effector cells (squares, n = 3) and CD4⁺CD25⁺ WT Treg cells (circle, n = 3) or CD4⁺CD25⁺<i>gzmA</i>^<i>-/-</i> Treg cells (triangle, n = 3) from WT mice. (A) Body weight of the recipients was monitored daily. (B) Histopathological investigations of liver, small and large intestine of mice sacrified after 3 weeks. (C) Histopathological GvHD scoring 3 weeks after transplantation were graded for severity of inflammation and degree of organ destruction resulting in an organ-specific cumulative pathology score. For statistical analysis student`s t-test was performed and p values <0.05 (*) were considered significant, while p<0.01 (**) and p<0.001 (**) were considered highly significant.</p

<i>GzmA</i>^<i>-/-</i> Tregs show no phenotypic alteration with respect to activation and migration.

<p>WT Tregs (white bars) and <i>gzmA</i>^<i>-/-</i> Tregs (grey bars) were isolated from spleen (A) and peripheral lymph nodes (B) and analyzed by FACS. Expression values were calculated as a percentage of the CD4⁺ T lymphocyte population and mean values are presented as bar graphs. Students t-test did not reveal any significant differences between WT and <i>gzmA</i>^<i>-/-</i> Tregs. Results are shown for n = 3 WT and <i>gzmA</i>^<i>-/-</i> mice each.</p

<i>GzmA</i>^<i>-/-</i> Tregs home efficiently to secondary lymphoid organs.

<p>CD4⁺ (A) and CD4⁺CD25⁺ Tregs (B) were isolated from spleen and peripheral lymph node from wildtype (WT; n = 3) and <i>gzmA</i>^<i>-/-</i> mice (n = 3) and analyzed by FACS. Expression values were calculated as a percentage of the T lymphocyte population and mean values are presented as bar graphs. Students t-test did not reveal any significant differences between WT and <i>gzmA</i>^<i>-/-</i> Tregs.</p