Browsing by Author "Mahdaviani, Seyed Alireza"

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Clinical, immunological, molecular and therapeutic findings in monogenic immune dysregulation diseases: Middle East and North Africa registry
(Academic Press Inc Elsevier Science, 2022-11-01) Jamee, Mahnaz; Azizi, Gholamreza; Baris, Safa; Karakoc-Aydiner, Elif; Ozen, Ahmet; Kilic, Sara S.; Kose, Hulya; Chavoshzadeh, Zahra; Mahdaviani, Seyed Alireza; Momen, Tooba; Shamsian, Bibi Shahin; Fallahi, Mazdak; Sharafian, Samin; Gulez, Nesrin; Aygun, Ayse; Karaca, Neslihan Edeer; Kutukculer, Necil; Al Sukait, Nashat; Al Farsi, Tariq; Al-Tamemi, Salem; Khalifa, Nisreen; Shereen, Reda; El-Ghoneimy, Dalia; El-Owaidy, Rasha; Radwan, Nesrine; Alzyoud, Raed; Barbouche, Mohamed-Ridha; Ben-Mustapha, Imen; Mekki, Najla; Rais, Afef; Boukari, Rachida; Belbouab, Reda; Djenouhat, Kamel; Tahiat, Azzeddine; Touri, Souad; Elghazali, Gehad; Al-Hammadi, Suleiman; Shendi, Hiba Mohammed; Alkuwaiti, Amna; Belaid, Brahim; Djidjik, Reda; Artac, Hasibe; Adeli, Mehdi; Sobh, Ali; Elnagdy, Marwa H.; Bahgat, Sara A.; Nasrullayeva, Gulnara; Chou, Janet; Rezaei, Nima; Al-Herz, Waleed; Geha, Raif S.; Abolhassani, Hassan; KILIÇ GÜLTEKİN, SARA ŞEBNEM; KÖSE, HÜLYA; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı/Çocuk Alerji ve İmmünoloji Bilim Dalı.; 0000-0002-5727-4075 ; JHC-2536-2023; LBH-2414-2024
Monogenic immune dysregulation diseases (MIDD) are caused by defective immunotolerance. This study was designed to increase knowledge on the prevalence and spectrum of MIDDs, genetic patterns, and outcomes in Middle East and North Africa (MENA). MIDD patients from 11 MENA countries (Iran, Turkey, Kuwait, Oman, Algeria, Egypt, United Arab Emirates, Tunisia, Jordan, Qatar, and Azerbaijan) were retrospectively evaluated. 343 MIDD patients (58% males and 42% female) at a median (IQR) age of 101 (42-192) months were enrolled. The most common defective genes were LRBA (23.9%), LYST (8.2%), and RAB27A (7.9%). The most prevalent initial and overall manifestations were infections (32.2% and 75.1%), autoimmunity (18.6% and 41%), and organomegaly (13.3% and 53.8%), respectively. Treatments included immunoglobulin replacement therapy (53%), hematopoietic stem cell transplantation (HSCT) (14.3%), immunosuppressives (36.7%), and surgery (3.5%). Twenty-nine (59.2%) patients survived HSCT. Along with infectious complications, autoimmunity and organomegaly may be the initial or predominant manifestations of MIDD.
Human TYK2 deficiency: Mycobacterial and viral infections without hyper-ige syndrome
(Rockefeller Univ Press, 2015-09-21) Kreins, Alexandra Y.; Ciancanelli, Michael J.; Okada, Satoshi; Kong, Xiao-Fei; Ramirez-Alejo, Noe; Kılıç, Sara Şebnem; El Baghdadi, Jamila; Nonoyama, Shigeaki; Mahdaviani, Seyed Alireza; Ailal, Fatima; Bousfiha, Aziz; Mansouri, Davood; Nievas, Elma; Ma, Cindy S.; Rao, Geetha; Bernasconi, Andrea; Kuehn, Hye Sun; Niemela, Julie; Stoddard, Jennifer; Deveau, Paul; Cobat, Aurelie; El Azbaoui, Safa; Sabri, Ayoub; Lim, Che Kang; Sundin, Mikael; Avery, Danielle T.; Halwani, Rabih; Grant, Audrey V.; Boisson, Bertrand; Bogunovic, Dusan; Itan, Yuval; Moncada-Velez, Marcela; Martinez-Barricarte, Ruben; Migaud, Melanie; Deswarte, Caroline; Alsina, Laia; Kotlarz, Daniel; Klein, Christoph; Muller-Fleckenstein, Ingrid; Fleckenstein, Bernhard; Cormier-Daire, Valerie; Rose-John, Stefan; Picard, Capucine; Hammarstrom, Lennart; Puel, Anne; Al-Muhsen, Saleh; Abel, Laurent; Chaussabel, Damien; Rosenzweig, Sergio D.; Minegishi, Yoshiyuki; Tangye, Stuart G.; Bustamante, Jacinta; Casanova, Jean-Laurent; Boisson-Dupuis, Stephanie; KILIÇ GÜLTEKİN, SARA ŞEBNEM; Uludağ Üniversitesi/Tıp Fakültesi/Pediatrik İmmünoloji Anabilim Dalı; AAH-1658-2021
Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-alpha/beta, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17(+) T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-gamma, IL-28/29 (IFN-lambda), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-alpha/beta. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans.
Inherited and acquired immunodeficiencies underlying tuberculosis in childhood
(Wiley, 2015-03-01) Boisson-Dupuis, Stephanie; Bustamante, Jacinta; El-Baghdadi, Jamila; Camcioglu, Yildiz; Parvaneh, Nima; El Azbaoui, Safaa; Agader, Aomar; Hassani, Amal; El Hafidi, Naima; Mrani, Nidal Alaoui; Jouhadi, Zineb; Ailal, Fatima; Najib, Jilali; Reisli, İsmail; Zamani, Adil; Yosunkaya, Sebnem; Gülle-Girit, Saniye; Yıldıran, Alişan; Cipe, Funda Erol; Torun, Selda Hançerli; Metin, Ayşe; Atıkan, Başak Yıldız; Hatipoğlu, Nevin; Aydoğmuş, Çiğdem; Kılıç, Sara Şebnem; Doğu, Figen; Karaca, Neslihan; Aksu, Güzide; Kütükcüler, Necil; Keser-Emiroğlu, Melike; Somer, Ayper; Tanır, Gönül; Aytekin, Caner; Adimi, Parisa; Mahdaviani, Seyed Alireza; Mamishi, Setareh; Bousfiha, Aziz; Sanal, Ozden; Mansouri, Davood; Casanova, Jean-Laurent; Abel, Laurent; KILIÇ GÜLTEKİN, SARA ŞEBNEM; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Pediatrik İmmünoloji Anabilim Dalı.; 0000-0001-8571-2581; AAH-1658-2021
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN- immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey.
Monogenic mutations differentially affect the quantity and quality of t follicular helper cells in patients with human primary immunodeficiencies
(Mosby-elsevier, 2015-10-01) Ma, Cindy S.; Wong, Natalie; Rao, Geetha; Avery, Danielle T.; Torpy, James; Hambridge, Thomas; Bustamante, Jacinta; Okada, Satoshi; Stoddard, Jennifer L.; Deenick, Elissa K.; Pelham, Simon J.; Payne, Kathryn; Boisson-Dupuis, Stephanie; Puel, Anne; Kobayashi, Masao; Arkwright, Peter D.; El Baghdadi, Jamila; Nonoyama, Shigeaki; Minegishi, Yoshiyuki; Mahdaviani, Seyed Alireza; Mansouri, Davood; Bousfiha, Aziz; Blincoe, Annaliesse K.; French, Martyn A.; Hsu, Peter; Campbell, Dianne E.; Stormon, Michael O.; Wong, Melanie; Adelstein, Stephen; Smart, Joanne M.; Fulcher, David A.; Cook, Matthew C.; Phan, Tri Giang; Stepensky, Polina; Boztug, Kaan; Kansu, Aydan; Ikinciogullari, Aydan; Baumann, Ulrich; Beier, Rita; Roscioli, Tony; Ziegler, John B.; Gray, Paul; Picard, Capucine; Grimbacher, Bodo; Warnatz, Klaus; Holland, Steven M.; Casanova, Jean-Laurent; Uzel, Gulbu; Tangye, Stuart G.; Kılıç, Sara Şebnem; KILIÇ GÜLTEKİN, SARA ŞEBNEM; Bursa Uludağ Üniversitesi/Tıp Fakültesi/İmmunoloji Anabilim Dalı.; 0000-0001-8571-2581
Background: Follicular helper T (T-FH) cells underpin T cell-dependent humoral immunity and the success of most vaccines. T-FH cells also contribute to human immune disorders, such as autoimmunity, immunodeficiency, and malignancy. Understanding the molecular requirements for the generation and function of T-FH cells will provide strategies for targeting these cells to modulate their behavior in the setting of these immunologic abnormalities.Objective: We sought to determine the signaling pathways and cellular interactions required for the development and function of T-FH cells in human subjects.Methods: Human primary immunodeficiencies (PIDs) resulting from monogenic mutations provide a unique opportunity to assess the requirement for particular molecules in regulating human lymphocyte function. Circulating follicular helper T (cT(FH)) cell subsets, memory B cells, and serum immunoglobulin levels were quantified and functionally assessed in healthy control subjects, as well as in patients with PIDs resulting from mutations in STAT3, STAT1, TYK2, IL21, IL21R, IL10R, IFNGR1/2, IL12RB1, CD40LG, NEMO, ICOS, or BTK.Results: Loss-of-function (LOF) mutations in STAT3, IL10R, CD40LG, NEMO, ICOS, or BTK reduced cT(FH) cell frequencies. STAT3 and IL21/R LOF and STAT1 gain-of-function mutations skewed cT(FH) cell differentiation toward a phenotype characterized by overexpression of IFN-gamma and programmed death 1. IFN-gamma inhibited cT(FH) cell function in vitro and in vivo, as corroborated by hypergammaglobulinemia in patients with IFNGR1/2, STAT1, and IL12RB1 LOF mutations.Conclusion: Specific mutations affect the quantity and quality of cT(FH) cells, highlighting the need to assess T-FH cells in patients by using multiple criteria, including phenotype and function. Furthermore, IFN-gamma functions in vivo to restrain T-FH cell-induced B-cell differentiation. These findings shed new light on T-FH cell biology and the integrated signaling pathways required for their generation, maintenance, and effector function and explain the compromised humoral immunity seen in patients with some PIDs.