Article
Allergy
Elma Isela Fuentes-Lara, Gabriel Emmanuel Arce-Estrada, Abner Bojalil-Cabildo, Marco Antonio Yamazaki-Nakashimada, Sara Elva Espinosa-Padilla, Luisa Berenise Gamez-Gonzalez, Rosa Maria Nideshda Ramirez-Uribe, Omar Josue Saucedo-Ramirez, Laura Berron-Ruiz
Summary: This study reports the clinical and immunological characteristics of six Mexican patients diagnosed with LAD-1, highlighting atypical manifestations not described in other countries and emphasizing the importance of flow cytometry in the diagnosis of LAD-1.
ALLERGOLOGIA ET IMMUNOPATHOLOGIA
(2023)
Article
Immunology
Ismail Yaz, Begum Ozbek, Hacer Neslihan Bildik, Cagman Tan, Sevil Oskay Halacli, Elif Soyak Aytekin, Saliha Esenboga, Sukru Cekic, Sara Sebnem Kilic, Ozlem Keskin, Karin Leeuwen, Dirk Roos, Deniz Cagdas, Ilhan Tezcan
Summary: Leukocyte adhesion deficiency type I is a rare immunodeficiency disorder caused by mutations in the ITGB2 gene. Patients often have early diagnosis and consanguineous parents. Clinical features include delayed cord separation and leukocytosis. Genetic evaluation reveals various ITGB2 gene variants, with some patients undergoing hematopoietic stem cell transplantation.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2021)
Article
Allergy
Mohammad Reza Fazlollahi, Amir Ali Hamidieh, Leila Moradi, Raheleh Shokouhi Shoormati, Nastaran Sabetkish, Behnaz Esmaeili, Mohsen Badalzadeh, Zahra Alizadeh, Somayeh Shamlou, Masoud Movahedi, Maryam Mahloujirad, Anahita Razaghian, Saba Arshi, Mohammad Gharagozlou, Arash Kalantari, Mohammad Hassan Bemanian, Mojgan Safari, Marzieh Heidarzadeh Arani, Mohammad Nabavi, Nima Parvaneh, Mahnaz Sadeghi-Shabestari, Maryam Behfar, Nasrin Behniafard, Roya Sherkat, Javad Ahmadian Heris, Mansoureh Shariat, Roshanak Radmehr, Massoud Houshmand, Anoshirvan Kazemnejad, Anne Molitor, Raphael Carapito, Seiamak Bahram, Zahra Pourpak, Mostafa Moin
Summary: This study assessed the clinical, laboratory, and genetic findings of 69 LAD-I patients and emphasized the importance of early diagnosis and physicians' awareness of the disease. The results showed that delayed umbilical cord separation and skin ulcers were common clinical symptoms, and genetic analysis identified multiple mutations in the ITGB2 gene.
PEDIATRIC ALLERGY AND IMMUNOLOGY
(2023)
Article
Cell Biology
Lai Wen, Alex Marki, Zhihao Wang, Marco Orecchioni, Jeffrey Makings, Monica Billitti, Erpei Wang, Sujit S. A. Suthahar, Kenneth Kim, William B. Kiosses, Zbigniew Mikulski, Klaus Ley
Summary: This study generated a humanized beta(2) integrin knockin mouse model to study its in vivo activation. The results showed that beta(2) integrins play an important role in leukocyte recruitment and neutrophil adhesion.
Article
Immunology
Serife Erdem, Sule Haskologlu, Yesim Haliloglu, Huriye Celikzencir, Elif Arik, Ozlem Keskin, Sevgi Bilgic Eltan, Esra Yucel, Halit Canatan, Huseyin Avcilar, Ebru Yilmaz, Alper Ozcan, Ekrem Unal, Musa Karakukcu, Mehmet Halil Celiksoy, Sara Sebnem Kilic, Ayca Demir, Ferah Genel, Nesrin Gulez, Mustafa Yavuz Koker, Ahmet Oguzhan Ozen, Safa Baris, Ayse Metin, Sukru Nail Guner, Ismail Reisli, Sevgi Keles, Esin Figen Dogu, Kamile Aydan Ikinciogullari, Ahmet Eken
Summary: In this study, we investigated the impact of pathogenic ITGB2 mutations on Th17/Treg differentiation and functions, as well as innate lymphoid cell (ILC) subsets, in 15 Turkish LAD-1 patients and controls. Our findings revealed decreased Treg cell percentages and in vitro-differentiated induced Tregs from naive CD4+ T cells in LAD-1 patients, despite elevated absolute CD4+ cell counts. Elevated serum IL-23 levels and increased production of IL-17A by LAD-1 patient-derived PBMCs were observed. Moreover, higher percentages of CD18-deficient Th17 cells and elevated ILC3 subset were detected in LAD-1 patients. These findings suggest a type 3-skewed immunity and potential contribution to LAD-1-associated autoimmune symptoms.
CLINICAL IMMUNOLOGY
(2023)
Article
Chemistry, Medicinal
Xiaokun Hong, Kaiyuan Song, Mueed Ur Rahman, Ting Wei, Yan Zhang, Lin-Tai Da, Hai-Feng Chen
Summary: Leukocyte adhesion deficiency-1 (LAD-1) disorder is caused by deficiency or mutation of fi2 integrin, and phosphorylation on threonine 758 of fi2 integrin acts as a molecular switch inhibiting filamin binding. The regulation mechanism of site-specific phosphorylation at the atom level is still poorly understood. Molecular dynamics simulation and Markov state model were used to study the dynamic regulation pathway of phosphorylation and shed light on the pathogenesis of LAD-1 disease and drug development.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Review
Medicine, General & Internal
Anastasiia V. Bondarenko, Oksana R. Boyarchuk, Inga S. Sakovich, Ekaterina A. Polyakova, Alexander A. Migas, Aleksandra N. Kupchinskaya, Aleksandra Opalinska, Adam Reich, Liubov Volianska, Anna M. Hilfanova, Fedir I. Lapiy, Liudmyla I. Chernyshova, Alla P. Volokha, Dariia V. Zabara, Mikhail V. Belevtsev, Tatsiana V. Shman, Lyudmila V. Kukharenko, Mikhail V. Goltsev, Tatsiana G. Dubouskaya, Andrei Y. Hancharou, Weizhen Ji, Saquib Lakhani, Carrie L. Lucas, Olga V. Aleinikova, Svetlana O. Sharapova
Summary: Partial leukocyte adhesion deficiency type 1 (LAD-1) is a rare condition characterized by milder infectious symptoms and immune system imbalance, with an increased risk of autoinflammatory complications. In this case study, a 22-year-old female with LAD-1 was diagnosed at the age of 2 years and exhibited low expression of the CD18 protein. Despite a severe phenotype, the patient survived without hematopoietic stem cell transplantation and experienced a pregnancy complicated by a pyoderma gangrenosum-like lesion. CD18 expression showed variability throughout her life, indicating the possible involvement of other mechanisms.
CLINICAL CASE REPORTS
(2023)
Article
Dermatology
Aleksandra Opalinska, Adrian Burdacki, Konrad Kwasniak, Katarzyna Pogoda, Jacek Tabarkiewicz, Adam Reich
Summary: This article discusses the medical history and treatment experience of an anonymous patient diagnosed with LAD-1 and PG during pregnancy and the COVID-19 pandemic in a foreign country. The patient's dermatologists, immunologist, and diagnostician provide information on the epidemiology, genetics, diagnosis, morphologic manifestations, treatment, and prognosis in LAD-1. The diagnostic and therapeutic process of the patient is discussed in the latter part of the paper.
DERMATOLOGY AND THERAPY
(2021)
Article
Immunology
Yoji Sasahara, Taizo Wada, Tomohiro Morio
Summary: Patients with classical Wiskott-Aldrich syndrome (WAS) and leukocyte adhesion deficiency (LAD) type 1 showed lower levels of Th1 and Th2 cytokine production following exposure to antigen-presenting cells, with distinct clinical symptoms associated with each disease.
CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Motoi Yamashita, Shiori Eguchi, Dan Tomomasa, Takahiro Kamiya, Daiki Niizato, Noriko Mitsuiki, Takeshi Isoda, Hanako Funakoshi, Yuki Mizuno, Kentaro Okamoto, Tuan Minh Nguyen, Hidetoshi Takada, Masatoshi Takagi, Kohsuke Imai, Tomohiro Morio, Hirokazu Kanegane
Summary: Leukocyte adhesion deficiency type I (LAD-I) is a rare genetic immune disorder that can be cured with allogeneic hematopoietic cell transplant (HCT). In cases where ideal donors are unavailable, HLA-haploidentical HCT with posttransplant cyclophosphamide (PT-CY) can be a safe and effective alternative.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Nezihe Koeker, Ihsan Deveci, Karin van Leeuwen, Sinan Akbayram, Dirk Roos, Taco W. Kuijpers, Mustafa Yavuz Koker
Summary: This study reports on two families with clinical features of LAD-III, identifying two novel mutations in the FERMT3 gene. The findings have important implications for understanding the pathogenesis of LAD-III.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Review
Medical Laboratory Technology
V. E. R. O. N. I. C. A. VILLANUEVA, X. I. A. O. B. O. LI, J. I. M. E. N. E. Z. H. A. F. E. E. Z. M. FARIDI, V. I. N. E. E. T. GUPTA
Summary: This article discusses the role of CD11b on leukocytes in lupus nephritis (LN) and emphasizes the importance of targeting integrin CD11b as a therapeutic approach for systemic lupus erythematosus (SLE) and LN.
TRANSLATIONAL RESEARCH
(2022)
Article
Immunology
Mehmet Halil Celiksoy, Mustafa Yavuz Koker, Alper Gezdirici, Sevil Ozsoy, Baris Malbora, Songul Gungor
Summary: Leukocyte adhesion deficiency is a rare primary immunodeficiency that has been categorized into different types, with clinical features including recurrent bacterial and fungal infections. Flow cytometry is a useful tool for rapid diagnosis of the disease, and CD18 expression levels are also associated with the severity of the disease in patients.
IMMUNOLOGIC RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Richard H. Smith, Hanan Bloomer, Danielle Fink, Keyvan Keyvanfar, Md Nasimuzzaman, Fatima Sancheznieto, Roop Dutta, Kacey Guenther Bui, Luigi J. Alvarado, Thomas R. Bauer, Dennis D. Hickstein, David W. Russell, Punam Malik, Johannes C. M. van der Loo, Steven L. Highfill, Douglas B. Kuhns, Mehdi Pirooznia, Andre Larochelle
Summary: This study provides pre-clinical evidence of the therapeutic usefulness of a foamy virus vector (FVV) for correcting genetic defects in LAD-1. Results showed that transduced cells displayed improvements in cellular chemotactic defects associated with LAD-1, and transplantation of vector-transduced cells in mice resulted in long-term engraftment. Vector insertion site analysis revealed no genotoxicity. These findings support the development of FVVs for ex vivo gene therapy of LAD-1.
HUMAN GENE THERAPY
(2022)
Article
Dentistry, Oral Surgery & Medicine
Sethumanjusha Saranu, Yalamanchili Samata, Nunsavathu Purnachandra Rao Naik, Garikipati Anoop
Summary: This paper presents a case of leukocyte adhesion deficiency in an 18-year-old girl and provides a brief literature review, highlighting the importance of considering LAD in patients with persistent periodontal problems.
JOURNAL OF INDIAN ACADEMY OF ORAL MEDICINE AND RADIOLOGY
(2022)