Leukocyte Adhesion Defect Research Articles

Transient Hyperleukocytosis in One of the Extreme Preterm Twins: A Case Report with Review of Literature

Background: Although physiological leukocytosis is known in premature neonates, hyperleukocytosis (total leukocyte count more than 100 × 103 /µL) is rarely seen. Commonly known disorders leading to hyperleukocytosis include leukemia, leukocyte adhesion defect, and myeloproliferative disorders. Transient hyperleukocytosis of unidentified etiology or attributed to sepsis has been rarely reported. Clinical Description: One of the extremely preterm twins (delivered at 26 weeks gestation) developed hyperleukocytosis on day 3 of life, without any evidence of blast cells on the peripheral smear, with normal C-reactive protein levels, while Twin 2 had normal leukocyte counts. Management and Outcome: Twin 1 was managed conservatively with mechanical ventilation, supportive care, and broad-spectrum antibiotics. His total leukocyte counts started reducing since day 5 of life and returned to normal after day 18, although he required prolonged respiratory support due to bronchopulmonary dysplasia (BPD). The other twin with a normal leukocyte count had a less difficult course and did not develop BPD. The twins being dichorionic-diamniotic type, and the placental histopathology of Twin 1 showing evidence of chorioamnionitis (the placenta of the other twin was normal), the transient hyperleukocytosis of Twin 1 was attributed to chorioamnionitis. Conclusion: The presence of hyperleukocytosis in only one of the neonates of an extremely preterm delivery highlights the fact that some factors such as chorioamnionitis or early-onset sepsis may contribute to this condition, which is transient, and resolves with supportive conservative care.

Molecular profile of patients with inborn errors of immunity from Nepal

Background and AimsInborn errors of immunity (IEIs) are increasingly being diagnosed in various regions of the world. There are significant challenges in the diagnosis and treatment of IEIs in resource-limited countries. With the availability of one immunologist and increasing awareness, IEIs are diagnosed with increasing frequency and accuracy in Nepal. IEIs are also being evaluated in children presenting with autoimmune manifestations. We describe the profile of patients diagnosed with IEIs in Nepal during 2020–2022. MethodsRecords of all patients with IEIs who were diagnosed and treated at our tertiary care center in Nepal from August 2020 to April 2022 were analysed. Lead author (DB) has examined and diagnosed all cases. IEIs were diagnosed based on the European Society for Immunodeficiencies (ESID) diagnostic criteria and genetic analysis. ResultsThirty-two patients with IEI (19 boys; 13 girls) and 801 children with autoimmune disorders were diagnosed during the study period. Genetic analysis was done on 18 patients. The diagnostic profile of the patients includes patients with chronic granulomatous disease, X-linked agammaglobulinemia, severe combined immunodeficiency, Job syndrome, selective IgA deficiency, specific antibody deficiency, Wiskott-Aldrich Syndrome, CTLA4 deficiency, IPEX syndrome, IFN-IL12 axis defect, hereditary angioedema, MonoMac syndrome, ARPC1B deficiency, leukocyte adhesion defect, PAPA syndrome, autoimmune lymphoproliferative syndrome, ADA2 deficiency, early-complement deficiency lupus, familial cold auto-inflammatory syndrome, A20 haploinsufficiency, and Blau syndrome. Some patients succumbed before the scope of diagnosis. HSCT is planned for 3 patients. ConclusionsOur is the first report of genetically proven IEIs in Nepal. Logistic constraints coupled with a lack of awareness of IEIs among laity and pediatrician accounted for a missed diagnosis, late diagnosis, and poor outcomes in resource-limited settings. Antimicrobial prophylaxis reduced the incidence of breakthrough infections. The lack of HSCT facilities precludes definitive treatment of many IEIs.

Tratamiento anestésico de la neuromiotonía. Descripción de un caso

The importance of neutrophils in fighting infections is clearly evidenced by “Experiments of Nature,” in which various gene mutations cause quantitative and qualitative abnormalities in the neutrophils. In such conditions, patients will suffer from infancy with life-threatening infections that must be treated promptly. In many cases delay in diagnosis and therapy may have serious consequences including death. This article focuses on severe congenital neutropenia, chronic granulomatous disease, leukocyte adhesion defects, and leukocyte motility abnormalities—all conditions that are related to congenital defects of the phagocytes.

Haematopoietic Stem Cell Transplantation (HSCT) for Primary Immune System Disorders in Children: A Single Centre Experience.

To determine the outcomes of allogeneic HSCT in children with primary immune system disorders (PID). Descriptive Cross-sectional study. Place and Duration of the Study: Armed Forces bone marrow transplant centre / National Institute of Bone Marrow Transplant (AFBMTC / NIBMT), Rawalpindi, Pakistan, from October 2012 to December 2021. Data of all cases undergoing HSCT for immune system disorders were analysed for variables affecting outcome and overall survival in the first 180 days after allogeneic HSCT. All patients presenting to AFBMTC / NIBMT with PID, age <12 years. Patients with organ dysfunction secondary to repeated infections were excluded from the study. Data of all patients and their donors undergoing HSCT for immune system disorders were analysed for variables affecting outcome and overall survival in the first 180 days after allogeneic bone marrow transplant. Neutrophil engraftment was defined as absolute neutrophil count ≥0.5 × 109/L for 3 consecutive days, while platelet engraftment as platelet count ≥20 × 109/L without platelet transfusion for one week. Overall survival (OS) was taken as time from the date of HSCT till day + 180 post-transplant. A total of 42children including 29 boys and 13 girls underwent HSCT for PID. The mean age was 2.1±2.8 years. Underlying diagnosis was haemophagocytic lymphohistiocytosis (HLH), severe immune deficiency (SCID), leukocyte adhesion defect (LAD), X-linked agammaglobulinemia, chronic granulomatous disease (CGD) and Job's syndrome in 18 (42.9%), 16 (38.1%), 3(7.1%), 2 (4.8%), 2 (4.8%) and 1 (2.4%) patients respectively. Thirty-one (73.8%) children had fully HLA-matched donors while 11 (26.2%) had haplo-matched donors. Major immediate post-transplant complications were febrile neutropenia, mucositis and SOS/VOD in 31 (73.8%), 9 (21.4%) and 4 (10.0%) cases, respectively. Eight (19.0%) had CMV reactivation, acute GVHD was seen in 17 (40.4%) cases, while 1 (2.3%) case had chronic GVHD. Twelve (28.6%) patients died, out of which 5 had graft failure, 3 had VOD, 2 had pneumonia, 1 had severe GVHD, and 1 died due to seizures. Overall survival (OS) in this study was 71.4% with survival reaching up to 80.6% in fully matched HSCT. HLH and SCID were the commonest immune disorders requiring HSCT. Graft failure leading to neutropenic sepsis was the commonest cause of mortality. OS was better in fully matched HSCT as compared to haplo-identical HSCT. Immune deficiency, Severe combined immunodeficiency, Haematopoietic stem cell transplantation.

Hematopoietic stem cell Transplantation in Children with very Early Onset Inflammatory Bowel Disease Secondary to Monogenic Disorders of immune-dysregulation.

Background: Very early-onset inflammatory bowel disease (VEOIBD) is defined as IBD in children under six years of age. We present outcome data of hematopoietic stem cell transplantation (HSCT) in the above children. Patients and methods: We performed a retrospective study in children under six years of age who underwent HSCT for VEOIBD with an identified monogenic disorder from December 2012 to December 2020. Results: Of the 25 children included, the underlying diagnosis was IL10R deficiency (n = 4), Wiskott-Aldrich syndrome (n = 4), Leukocyte adhesion defect (n = 4), Hyper IgM syndrome (n = 3), Chronic granulomatous disease (n = 2), and one each with XIAP deficiency, severe congenital neutropenia, Omenn syndrome, Hyper IgE syndrome, Griscelli syndrome, MHC Class II deficiency, LRBA deficiency, and IPEX syndrome. Donors included a matched family donor in 10(40%); a matched unrelated donor in 8 (32%), haploidentical in 7 (28%) (T depleted 16%, T replete with post-transplant cyclophosphamide12%). Conditioning was myeloablative in 84% ofHSCTs. We documented engraftment in 22 (88%) children, primary graft failure in 2 children (8%), mixed chimerism in 6 (24%) children with mortality in 4/6 children. Children with a sustained chimerism of > 95% did not have recurrence of any features of IBD. Overall survival was 64%, with a median follow-up of 55 months. Mixed chimerism was associated with a significantly increased risk of mortality (p-value = 0.001). Conclusions: VEOIBD caused by monogenic disorders can be offered HSCT. Early recognition, optimal supportive care, and complete chimerism are essential components to achieving survival.

Three novel homozygous ITGB2 mutations among two patients with leukocyte adhesion defect type-1: Two case reports

BACKGROUNDA leukocyte adhesion defect (LAD) is a rare primary immunodeficiency disorder. LAD type 1 (LAD-1) is the most common, which is caused by ITGB2 mutation resulting in dysfunction of β2 integrin, which impairs leukocyte adherence to the endothelium.CASE SUMMARYThe first two cases of LAD-1 in Thailand presented with recurrent omphalitis, soft tissue infection, marked leukocytosis, and neutrophilia. One patient experienced delayed umbilical cord separation. Mutation analysis was performed by direct DNA sequencing of the ITGB2 gene. The results revealed two novel homozygous missense mutations, c.920C>T (p.Leu307Pro) in exon 8 and c.758G>A (p.Arg253His) in exon 7, and one novel homozygous nonsense mutation, c.262C>T (p.Gln88Ter) in exon 4, in the genomic DNA of the first and second patients, respectively. Heterozygous mutations were identified in the parents of both patients, suggesting a carrier status. The patients were administered intravenous antibiotics for infections with good clinical responses. Hematopoietic stem cell transplantation could not be performed due to the unavailability of matched donors. However, a significant decline in infections was observed after antibiotic prophylaxis. Several follow-up visits were conducted for both patients. They are currently 6 years old.CONCLUSIONMolecular analysis is essential for definitive diagnosis, early treatment implementation, and prevention of LAD-1 in future pregnancy.

Leukocyte adhesion defect: Clinical correlation with integrin expression and genetics

Objectives: Leucocyte adhesion defect 1 (LAD1) is an autosomal recessive defect in integrin expression. In this study we present a case series of 19 children with LAD1. We analysed their clinical and laboratory data and correlated it with integrin expression and underlying genetic defect. Material and Methods: Retrospective case record study of all children diagnosed with LAD1 between 2012 and 2021. Results: Ten females and 9 males were included. Eight cases were born of consanguineous marriage. 78% (15/19) had disease onset within one year of life and 8 of them were neonates. Neonates with LAD1 commonly presented with omphalitis, late-onset sepsis and respiratory infections (RTI). Most common organism isolated from blood was pseudomonas (4/8). CD11/CD18-expression ranged from severely reduced (6/8) to moderately reduced (2/8) but disease was uniformly fatal in the 7/8 patients who could not undergo hematopoietic stem cell transplant (HSCT). Seven children presented between 1month and 1year of age with RTI, bacterial sepsis and soft tissue abscess. Four expired, 1 survived after HSCT and 2 were alive at last follow up. CD11/CD18-expression ranged between 0-1.6% except in 2 cases. One child with 11%-expression is alive without transplant. Another child had 0%-CD11 but 17%-CD18-expression with very low MFI (mean florescence intensity). She succumbed at 20 months of age with perianal abscess, sepsis and RTI but prior to this fatal episode she developed autoimmune cutaneous lesions with lymphocytic infiltration. Four children presented beyond infancy. Median age at onset of symptom was 2 years with skin abscess, oral ulcers, severe periodontitis with tooth loss and pyogenic arthritis. Three of them survived without HSCT, 1 was alive at last follow up. CD11/CD18-expression ranged from 20-32% in these children. Details of cord separation was available in 17 cases and it was delayed (beyond 2 weeks of life) in 9 children. Of the 17 cases with genetic analysis of ITGB2 gene, 16 had a homozygous and 1 had compound heterozygous variant. (nonsense: 2; splice site variants:5; 8: missense variants; 2: deletion). Conclusion: Disease onset less than 1 year age was fatal, irrespective of CD11/CD18 expression. Integrin expression levels beyond 20% and splice site mutation were associated with 100% survival without HSCT but were not event free. Pseudomonas sepsis is the commonest infection in LAD1 neonates. Between 1month to 1year, RTI and gram-negative sepsis dominated and beyond 1st-year skin/perianal abscess was common. Delayed separation of cord was present only in 52% of cases.

Utility of targeted next generation sequencing for inborn errors of immunity at a tertiary care centre in North India

Inborn errors of immunity (IEI) are a heterogeneous group of monogenic disorders that include primary immunodeficiency’s and other disorders affecting different aspects of the immune system. Next-Generation Sequencing (NGS) is an essential tool to diagnose IEI. We report our 3-year experience in setting up facilities for NGS for diagnosis of IEI in Chandigarh, North India. We used a targeted, customized gene panel of 44 genes known to result in IEI. Variant analysis was done using Ion Reporter software. The in-house NGS has enabled us to offer genetic diagnoses to patients with IEI at minimal costs. Of 121 patients who were included pathogenic variants were identified in 77 patients. These included patients with Chronic Granulomatous Disease, Severe Combined Immune Deficiency, leukocyte adhesion defect, X-linked agammaglobulinemia, Ataxia Telangiectasia, Hyper-IgE syndrome, Wiskott Aldrich syndrome, Mendelian susceptibility to mycobacterial diseases, Hyper-IgM syndrome, autoimmune lymphoproliferative syndrome, and GATA-2 deficiency. This manuscript discusses the challenges encountered while setting up and running targeted NGS for IEI in our unit. Genetic diagnosis has helped our patients with IEI in genetic counselling, prenatal diagnosis, and accessing appropriate therapeutic options.

Leukocyte Adhesion Defects Type III

Leukocyte adhesion defect (LAD) Type III is an extremely rare disease, which presents with severe infections and a Glanzmann thrombasthenia-like bleeding phenotype. A 2-year-old male child with LAD Type III with recurrent mucosal bleeding and relatively few infections is presented to highlight this novel presentation. The rare association of primary immunodeficiency and platelet functional disease is described.

A novel ITGB2 variant with long survival in patients with leukocyte adhesion defect type-I

Leukocyte adhesion deficiency is an autosomal recessive primary immunodeficiency that has been divided into three types: LAD1 (beta-2 integrin (CD18) family deficiency/defect), LAD2 (absence of fucosylated carbonhydrate ligands for selectins) and LAD3 (defective activation of all beta integrins). However, recently LAD4 has been described in cystic fibrosis patients, with a defect in integrin activation reported in monocytes. LAD-I is the most common type and prevalence of 1 in 1,000,000 live births. Clinical features of LAD patients are recurrent bacterial and fungal infections, omphalitis with delayed umbilical stump separation, significant leukocytosis especially neutrophilia during infection periods, impaired pus formation, and delayed traumatic or surgical wound healing. Flow cytometry is considered a useful tool for rapid diagnosis of the disease. The study of CD18 and CD11 (a, b, c) expression patterns in peripheral blood leukocytes helps to distinguish different phenotypes of LAD-I. In general, patients with ≥ 2% CD18 expression tend to have a less severe infection and often survive until adulthood, whereas < 2% CD18 expression often results in death in infancy. In this case report, three siblings, 10, 15, and 17years old, diagnosed with leukocyte adhesion defect type 1 in adolescence age group, are presented.

The Prevalence of Atopic Manifestations in 313 Iranian Patients with Inborn Errors of Immunity

Introduction: Inborn errors of immunity (IEIs) are rare inherited disorders with a broad spectrum of manifestations. Here, we aimed to delineate the atopy burden in a cohort of patients with IEIs. Methods: 313 patients with IEIs were enrolled in the study within a 9-years period, and data were collected via a questionnaire. All statistical analyses were performed using SPSS software (v. 25.0, Chicago, IL, USA). The statistical significance level was set at p < 0.05. Results: Overall, 51 out of 313 (16.3%) patients were identified to have atopic manifestations. Food allergy was detected in 34 (10.2%), atopic dermatitis in 21 (6.7%), as well as allergic asthma and allergic rhinitis each in 4 (1.3%) patients. The allergic disorders were reported as initial manifestations among 14 out of 35 (40.0%) atopic patients. Most of these 51 patients fell within the category of combined immunodeficiency (CID) (n = 38, 74.5%), followed by, severe CID (SCID) (n = 5, 9.8%), common variable immunodeficiency (n = 3, 5.9%), chronic granulomatous disease (n = 3, 5.9%), selective IgA deficiency (n = 1, 2.0%), and leukocyte adhesion defect (n = 1, 2.0%). No patient with Mendelian susceptibility to mycobacteria was found to have atopic manifestation. Atopic dermatitis (p = 0.001) and food allergy (p < 0.001) were both significantly higher in patients with CID than in other IEI groups. Among atopic patients with CID and SCID, food allergy and atopic dermatitis were the most prevalent comorbidities. Discussion/Conclusion: Atopic diseases may contribute to the clinical picture of IEIs, particularly in patients with CID. Atopy in association with other warning signs of IEIs increases the possibility of an underlying IEI.

LEUKOCYTE ADHESION DEFECT: A CASE SERIES OF 3 CHILDREN

Leukocyte adhesion defect (LAD) is a rare, autosomal recessive primary immunodeficiency disorder of phagocytes, in which there is defective aggregation at the site of infection due to the absence of surface integrins. Diagnosis is based primarily on flowcytometric analysis of neutrophils for the surface expression of CD11, CD18 and CD15s. We describe here a case series of 3 children presented to us within a period of one year and diagnosed as LAD. Diagnosis was made on the basis of clinical features and simple laboratory investigations.

The physiological and pathological roles and applications of sialyl Lewis x, a common carbohydrate ligand of the three selectins

In the past decades, the roles of carbohydrates in living organisms and their potential use in many fields have been extensively investigated. Sialyl Lewis x (sLex), a member of body carbohydrate, is an inherent blood-type tetrasaccharide on the surface of different cells, the lymphocyte, neutrophil, some T cells, multiple tumor cells and so on. SLex is a common ligand of the three selectins, L-selectin, E-selectin and P-selectin, and plays important roles in multiple physiological phenomenas by interacting with selectins. Under normal physiological conditions, sLex can affect the immune process and fertilization process. Lower expression of sLex could cause leukocyte adhesion defects (LAD) II. Overexpression of sLex on the other hand has been linked to several cancers including melanoma, breast, pancreatic, liver, lung, head and neck, ovarian, bladder carcinomas and some blood disease including Hodgkin disease, some B cell chronic lymphocytic leukemias, acute lymphoblastic leukemias, and most acute nonlymphocytic leukemias. This paper mainly reviews the physiological functions and pathological effects of sLex and its applications in disease diagnosis, drug delivery, gene transfer and medical molecular imaging. We aim to help researchers and other readers quickly grasp the physiological and pathological roles and its medical applications of sLex, and give some suggestions for research directions.

Direct Rap1/Talin1 interaction regulates platelet and neutrophil integrin activity in mice

AbstractTargeting Talin1 to the plasma membrane is a crucial step in integrin activation, which in leukocytes is mediated by a Rap1/RIAM/Talin1 pathway, whereas in platelets, it is RIAM independent. Recent structural, biochemical, and cell biological studies have suggested direct Rap1/Talin1 interaction as an alternative mechanism to recruit Talin1 to the membrane and induce integrin activation. To test whether this pathway is of relevance in vivo, we generated Rap1 binding–deficient Talin1 knockin (Tln13mut) mice. Although Tln13mut mice showed no obvious abnormalities, their platelets exhibited reduced integrin activation, aggregation, adhesion, and spreading, resulting in prolonged tail-bleeding times and delayed thrombus formation and vessel occlusion in vivo. Surprisingly, neutrophil adhesion to different integrin ligands and β2 integrin–dependent phagocytosis were also significantly impaired, which caused profound leukocyte adhesion and extravasation defects in Tln13mut mice. In contrast, macrophages exhibited no defect in adhesion or spreading despite reduced integrin activation. Taken together, our findings suggest that direct Rap1/Talin1 interaction is of particular importance in regulating the activity of different integrin classes expressed on platelets and neutrophils, which both depend on fast and dynamic integrin-mediated responses.

A patient with leukocyte adhesion defect

During inflammation, leukocytes play a key role in maintaining tissue homeostasis by elimination of pathogens and removal of damaged tissues. Leukocytes migrate to the site of inflammation by crawling over and through the blood vessel wall, into the tissue. Leukocyte adhesion deficiencies (LAD 1, LAD 2 and LAD 3) are caused by defects in the adhesion of leukocyte to the blood vessel wall due to mutations in the genes encoding b2 integrin, selectin and kindling-3, respectively. Patients experience recurrent none pus forming bacterial infections and neutrophilia, often preceded by delayed separation of umbilical cord. This case report describes a child who presented with umbilical sepsis followed by separation of the umbilical cord on day 15, and recurrent bacterial meningitis with high neutrophilia.

Novel mutations of ITGB2 induced leukocyte adhesion defect type 1

Objective: To investigate the pathogenic mechanism of two novel ITGB2 mutations in leukocyte adhesion defect type 1 (LAD1). Methods: The clinical history and blood sample of an 11 years old patient admitted to Affiliated Hospital of Qingdao University in August 2014 were collected. Expression of CD18 (encoded by ITGB2) was analyzed by flow cytometry. Novel ITGB2 mutations were identified by next-generation sequencing technology and confirmed by Sanger sequencing. The functional effect of ITGB2 mutations was detected by PolyPhen2. Expression vectors of both wild type and mutant ITGB2 were constructed and transfected into mammalian cells for analysis of protein stability and subcellular location. Results: The symptoms of the patient (recurrent infections, lowered alveolar ridge and hypodontia) supported the diagnosis of LAD1. Expression of CD18 on the leukocytes was significantly decreased (0.2%) compared with the control samples from the parents (paternal: 99.0%; maternal: 99.1%). The patient was identified to be compound heterozygous for ITBG2 c.954del G (novel mutation) and c.1802C>A (paternal originated). ITGB2 c.954 del G was confirmed to be a harmful frameshift mutation; ITGB2 c.1802C>A was also predicted to be harmful. In terms of protein stability. There was no significant difference between mutant D18 and wild type. However, subcellular location analysis showed the mutant D18 could not locate on cell membrane. Conclusion: The compound heterozygous of ITGB2 mutations (c.954del G and c.1802C>A) decreases the expression and impairs the location of CD18 on leukocytes, which leads to LAD1.

An Update on the Use of Immunomodulators in Primary Immunodeficiencies.

The genomic revolution in the past decade fuelled by breathtaking advances in sequencing technologies has defined several new genetic diseases of the immune system. Many of these newly characterized diseases are a result of defects in genes involved in immune regulation. The discovery of these diseases has opened a vista of new therapeutic possibilities. Immunomodulatory agents, a hitherto unexplored therapeutic option in primary immunodeficiency diseases have been tried in a host of these newly described maladies. These agents have been shown conclusively to favorably modulate immune responses, resulting in abatement of clinical manifestations both in experimental models and patients. While some of the treatment options have been approved for therapeutic use or have been shown to be of merit in open-label trials, others have been shown to be efficacious in a handful of clinical cases, animal models, and cell lines. Interferon γ is approved for use in chronic granulomatous disease (CGD) to reduce the burden of infection and and has a good long-term efficacy. Recombinant human IL7 therapy has been shown increase the peripheral CD4 and CD8 T cell counts in patients with idiopathic CD4. Anti-IL1 agents are approved for the management of cryopyrin-related autoinflammatory syndrome, and their therapeutic efficacy is being increasingly recognized in other autoinflammatory syndromes and CGD. Mammalian target of rapamycin (mTOR) inhibitors have been proven useful in autoimmune lymphoproliferative syndrome (ALPS) and in IPEX syndrome. Therapies reported to be potential use in case reports include abatacept in CTLA4 haploinsufficiency and LRBA deficiency, ruxolitinib in gain-of-function STAT1, tocilizumab in gain-of-function STAT3 defect, mTOR inhibitors in PIK3CD activation, magnesium in XMEN syndrome, and pioglitazone in CGD. Treatment options of merit in human cell lines include interferon α and interferon β in TLR3 and UNC-93B deficiencies, anti-interferon therapy in SAVI, and Rho-kinase inhibitors in TTC7A deficiency. Anti-IL17 agents have show efficacy in animal models of leukocyte adhesion defect (LAD) and ALPS. This topical review explores the use of various immunomodulators and other biological agents in the context of primary immunodeficiency and autoinflammatory diseases.

Leukocyte adhesion deficiency type III: clinical features and treatment with stem cell transplantation.

Leukocyte adhesion deficiency type III (LADIII) is an autosomal recessive disorder that presents with a severe leukocyte adhesion defect and a Glanzmann-type thrombocytopathy. Hematopoietic stem cell transplantation (HSCT)--the only definitive treatment for LADIII--appears to have a high rate of complications. In this study, we describe a new group of patients with LADIII, highlighting further clinical and immunologic aspects of this disease, and reevaluating the effectiveness of HSCT for its treatment. The patients had clinical and laboratory findings consistent with LADIII. Molecular analysis confirmed the presence of a mutation in the kindlin-3 gene. HSCT was carried out in 3 patients and was successful in 2. The diagnosis of LADIII should be considered in all patients who present with recurrent infections and a bleeding diathesis, regardless of the leukocyte count. LADIII is a primary immune deficiency, which can be successfully corrected by bone marrow transplantation if applied early in the course of the disease using appropriate conditioning.

Leukocyte adhesion defect: A rare cause of immunodeficiency

Leukocyte adhesion deficiency 1 (LAD-1) is a rare autosomal recessive disorder of leukocyte function due to integrin deficiency. It is characterized by recurrent bacterial and fungal infections and depressed inflammatory responses despite striking blood neutrophilia. Severe LAD usually presents early in infancy. Here, we report a case who presented late with symptoms of LAD-1 when compared with earlier reported cases and without the usually associated infections.

Congenital CMV With LAD Type 1 and NK Cell Deficiency

We report a rare case of congenital cytomegalovirus (CMV) in a patient who was subsequently diagnosed as leukocyte adhesion defect type 1 with natural killer cell deficiency. The clinical course was complicated by severe CMV pneumonitis during the newborn period. Thereafter the infant suffered from recurrent skin infections without pus formation, otitis media, and bronchopneumonia since 3 months of age. The patient had congenital CMV infection as urine and blood plasma was positive for CMV from day 12 onward. Neutrophil chemotaxis studies showed a decrease in directed chemotaxis. Neutrophils were dyspoetic and nonfunctional lacking HLA DR, CD11c, and CD18. Lymphocytes were polyclonal but lacked CD56, CD16, and surface membrane immunoglobulin.