Primary Immunodeficiency Research Articles

Linking Microbiota Profiles to Disease Characterization in Common Variable Immunodeficiency: The Case of Granulomatous-Lymphocytic Interstitial Lung Disease.

Background and objectives: Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by decreased immunoglobulins and recurrent infections, with non-infectious complications such as granulomatous-lymphocytic interstitial lung disease (GLILD) affecting up to 30% of patients. Methods: Using high-throughput 16S rRNA gene sequencing, salivary, sputum, and fecal microbiome from CVID patients with GLILD, comparing them to CVID patients without GLILD-with immune dysregulation (dCVID) and only infections (iCVID)-and healthy controls was analyzed. Results: A total of 41 CVID patients, 7 with GLILD, and 15 healthy donors were included. Global fecal biodiversity was significantly lower in GLILD patients compared to CVID subgroups and controls. GLILD patients harbored different specific bacterial communities in all niches, with some keystone species common to dCVID. Conchiformibius, Micrococcales, and Capnocytophaga are more frequent in the sputum of GLILD patients. Saliva in GLILD shows higher frequencies of Conchiformibius and Haemophilusparainfluenzae. Fecal samples from GLILD patients have higher levels of Gemella morbilorum, Lacticaseibacillus, and Cellulosimicrobium. A non-assigned Conchiformibius spp. is consistently associated with GLILD across different niches and could be a potential pathobiont or relevant microbiological marker for GLILD. Cluster network and correlation analyses show profound dysbiosis in the sputum, saliva, and feces of GLILD patients. Conclusions: These findings highlight significant microbiome alterations in CVID patients with GLILD, particularly in the respiratory tract, suggesting a possible link to both local and systemic immune dysregulation.

Insights into disease resilience and longevity: Hints from COVID-19 recovered nonagenarians and centenarians

The effects of aging on the organism manifest in various ways, including profound and complex changes in functioning patterns, responses to stimuli, and regenerative capacity. Nevertheless, it is remarkable that some elderly individuals maintain their health and functionality despite advanced age, showing resilience to environmental adversities, such as SARS-CoV-2 infection. In this study, we examined a unique cohort of 100 individuals older than 90 years, including centenarians, who recovered from COVID-19 before the availability of vaccines in Brazil. We performed whole-exome analyses and identified incidental findings in four participants. These findings included pathogenic variants associated with serious conditions, such as cancer predisposition and cardiovascular diseases. Specifically, variants were found in the RYR1, DSP, BRCA2, BRCA1, and TTN genes. Also, other two individuals were homozygous for rare variants in the TYK2 gene, related to primary immunodeficiencies. The significance of these findings is underscored by the fact that, despite carrying these rare variants, these individuals surpassed 90 years of age and survived the COVID-19 pandemic. This suggests the presence of genetic protective factors that contribute to longevity and resilience. Therefore, this study provides new insights into interpreting incidental findings in long-lived populations and raises important questions for clinical practice and the genetics of longevity.

Peripheral blood transcriptome analysis in sepsis-associated acute kidney injury

Sepsis-associated acute kidney injury (S-AKI) presents significant clinical challenges, necessitating deeper insights into its molecular mechanisms. We conducted a comprehensive analysis—including Principal Component Analysis (PCA), differential gene expression, KEGG pathway enrichment, and Gene Set Enrichment Analysis (GSEA)—to elucidate the underlying pathways involved in S-AKI. PCA revealed distinct clustering between S-AKI patients and controls, with differential gene expression identifying 1,759 significant genes (912 upregulated, 847 downregulated). Notable upregulated genes included CYP19A1 and LY6G6F, while downregulated genes encompassed LRP1B and SIGLEC8. KEGG analysis highlighted pathways related to adaptive immune responses and infection, such as “Th1 and Th2 cell differentiation" and "Primary immunodeficiency.” GSEA pinpointed "Neutrophil extracellular trap formation" as the most significantly enriched pathway, underscoring neutrophil-mediated responses in S-AKI. Our findings suggest potential molecular targets for diagnosis and therapeutic intervention, providing a foundation for future research and improved clinical outcomes.

Clinical Manifestations of Wiskott-Aldrich Syndrome in an Iranian Patient

Wiskott-Aldrich Syndrome (WAS) is an immunodeficiency disorder resulting from genetic mutations in the WAS protein (WASP) gene in the X chromosome, characterized by thrombocytopenia, eczema, and infections. This case report focused on a 12-year-old Iranian male with WAS with a history of Crohn’s disease, meningitis, and bilateral hernia. His WAS was diagnosed at age six with a hemizygous c.777+1 G>A mutation in the WASP gene. The patient was referred to our clinic with symptoms including fever, abdominal pain, thrombocytopenia, and elevated ESR. Clinical Imaging revealed a significant lung nodule align bronchiectasis, mild ascites, bilateral epididymitis, and lymphadenopathy. Nephrotic syndrome with proteinuria and low levels of albumin have been observed. After six months of receiving intravenous immunoglobulin (IVIG) therapy in addition to antibiotics and antivirals, the patient suffered from arthritis, edema, and fever. Our WAS patient presented the late comorbidity of renal involvement, which highlights the monitoring of this patient, such as those involved in chronic infections. Therefore, a precise treatment approach is needed to manage either the primary immunodeficiency or the late-discovered diseases.

Protective role of antibodies in enteric virus infections: Lessons from primary and secondary immune deficiencies.

Enteric viruses are the main cause of acute gastroenteritis worldwide with a significant morbidity and mortality, especially among children and aged adults. Some enteric viruses also cause disseminated infections and severe neurological manifestations such as poliomyelitis. Protective immunity against these viruses is not well understood in humans, with most knowledge coming from animal models, although the development of poliovirus and rotavirus vaccines has extended our knowledge. In a classical view, innate immunity involves the recognition of foreign DNA or RNA by pathogen recognition receptors leading to the production of interferons and other inflammatory cytokines. Antigen uptake and presentation to T cells and B cells then activate adaptive immunity and, in the case of the mucosal immunity, induce the secretion of dimeric IgA, the more potent immunoglobulins in viral neutralization. The study of Inborn errors of immunity (IEIs) offers a natural opportunity to study nonredundant immunity toward pathogens. In the case of enteric viruses, patients with a defective production of antibodies are at risk of developing neurological complications. Moreover, a recent description of patients with low or absent antibody production with protracted enteric viral infections associated with hepatitis reinforces the prominent role of B cells and immunoglobulins in the control of enteric virus.

Clinical and epidemiological aspects of primary immunodeficiencies in the Republic of Karakalpakstan

Studying the prevalence of primary immunodeficiency disorders (PID) is an important aspect of epidemiological research, as it allows for assessing the frequency of these diseases occurring in different regions. The distribution of PID may vary depending on ethnic background and geographical location. Information on the prevalence of PID at regional, national, and international levels enables a more accurate determination of the scale of the problem and the development of effective prevention and treatment strategies. Studying the epidemiological and clinical profile of congenital immune disorders (PID) in the Republic of Karakalpakstan is crucial for understanding the prevalence, age and gender structure, as well as the spectrum of nosological forms of these rare diseases. The aim of this study was to investigate the epidemiological and clinical characteristics of congenital immune disorders, primary immunodeficiencies in the Republic of Karakalpakstan. The study material consisted of data on patients receiving inpatient treatment at a multidisciplinary children’s hospital in the Republic of Karakalpakstan and those under the care of an allergist-immunologist in the outpatient clinic at district medical centers in the Republic of Karakalpakstan. The average delay in diagnosis from the onset of clinical manifestation of PID in the region was 2.7 years. It was found that the mortality rate was 2.8%. Screening tests for verifying PID in the diagnostic search stage included clinical and biochemical blood analyses, and determination of serum immunoglobulins. At the time of diagnosis, patients exhibited a significant decrease in IgG and IgA immunoglobulin levels. In addition to the disorder in the humoral branch of adaptive immunity, children with this disease showed a decrease in the absolute number of T lymphocytes. The data obtained from the study indicate insufficient diagnosis of primary immunodeficiencies in the Republic of Karakalpakstan, which may serve as a basis for the development of educational programs aimed at increasing awareness of primary immunodeficiencies. Further research and systematization of information on patients with primary immunodeficiencies are necessary for the development of regional programs for the implementation of screening diagnostics.

Secondary Hypogammaglobulinemia

Secondary hypogammaglobulinemia (SHG) is characterized by reduced immunoglobulin levels due to extrinsic causes, such as a medication or an acquired disease process, resulting in decreased immunoglobulin production or increased immunoglobulin loss. Most published reports of SHG refer to IgG hypogammaglobulinemia and data on isolated IgA or IgM hypogammaglobulinemia is limited. The common causes of SHG include medications, hematological malignancies, and conditions associated with protein loss. Hypogammaglobulinemia can increase the risk of infection, morbidity and mortality, particularly in patients who may already be immunocompromised due to their associated condition or use of immunosuppressive therapies. With growing use of immunosuppressive or immunomodulatory treatments that affect B-cells, it is increasingly important to assess and monitor for SHG. Treatment of the underlying condition or removal of the extrinsic factor often results in resolution of the SHG. A subset of patients presenting with autoimmune or malignant conditions can have a primary immunodeficiency (PID) or primary immune regulatory disorder. It is therefore important to consider both primary and secondary causes when assessing hypogammaglobulinemia. This article will review these common causes and discuss an approach to assessment and management of SHG.

Association between Infection and Calculated Globulin Level among Patients with Thymic Epithelial Tumor.

Background: Thymic epithelial tumors (TETs) are uncommon malignancies uniquely associated with autoimmunity and immunodeficiency. Previous studies among patients with primary immunodeficiency diseases have shown that a low calculated globulin (CG) level, obtained by subtracting albumin from total protein level, is associated with infection risk. We investigated this association among patients with TET. Methods: A cross-sectional retrospective study was performed based on electronic medical records of patients with TET treated during 2002-2024 at a tertiary care institution. For each patient, their lowest CG level and the date of occurrence were identified. The incidence of serious infection requiring hospitalization during 6 months before and 6 months after the index date was recorded. Multivariable Poisson regression models were constructed. Results: Among 101 TET patients, 96 patients (95%) had the information available to derive at least one CG level. The median lowest CG level was 2.65 g/dL (range 1.0-4.2). There were 33 serious infection episodes. Pneumonia was the most prevalent type of infection in 52% of episodes. In a multivariable analysis, a CG level below 2.0 was independently associated with the prevalence of infection with a prevalence ratio of 6.18 (95% CI: 3.12-12.23, p < 0.001). Furthermore, thymectomy was significantly associated with infection. Conclusions: Among patients with TET, a low CG level was associated with an increased prevalence of serious infections. Our limited experiences suggest that it is feasible to derive the CG level for most patients during routine clinical care.

Hypogammaglobulinemia in a child with atypical hemolytic-uremic syndrome

We present a unique clinical case of an atypical hemolytic-uremic syndrome in a child. The mutation in exon 6 of the CD46 gene (chr1:207940532G&gt;C) leads to a homozygous or hemizygous missense substitution. An 8-year-old girl was urgently hospitalized with symptoms of hemorrhagic syndrome and acute kidney injury. The child from the second pregnancy with an aggravated obstetric anamnesis, the first operative labor at the 38th week, who has an aggravated genealogical anamnesis. Initially, the disease developed in the guise of gastroenterological pathology: the girl had dyspeptic disorders, most likely associated with pathology of carbohydrate metabolism, also frequent infectious diseases and a lag in physical development. From the age of 4 years, the girl suffered from persistent hypoalbuminemia, hypoproteinemia and hypogammaglobulinemia, requiring replacement therapy with intravenous immunoglobulins. She was repeatedly examined in gastroenterological departments in Yekaterinburg and Moscow in 2021-2023, but no data concerning protein-losing enteropathies or primary immunodeficiency was obtained. Also, the whole-exome sequencing with result validation hasn’t confirmed an inherited etiology of the presumed congenital immune error. However, a CD46 gene mutation, associated with the development of hemolytic-uremic syndrome in some publications, was identified in the study. The signs of thrombotic microangiopathy were preceded by fever of unspecified etiology: microangiopathic hemolysis, thrombocytopenia, hyperazotemia, C3 consumption, proteinuria, and macrohematuria; hypercholesterolemia, protein metabolism disorder, increased transaminases, ferritin were also noted. According to the ultrasound of the kidneys there were diffuse changes in the parenchyma, decreased velocity indices of blood flow in both renal arteries at all levels. Differential diagnosis was carried out with thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, antinuclear form of atypical hemolytic-uremic syndrome, viral and bacterial infections, systemic pathology, antiphospholipid syndrome, and hemoblastosis. The girl didn’t need a renal replacement therapy. When complement-blocking therapy with eculizumab was initiated on vital indications, the signs of the disease were gradually eliminated. The prolonged absence of nephropathy in the child may indicate the diversity of the CD46 gene’s functions and different phenotypic manifestation of its mutations. Analysis of literature sources and detection of CD46 “environment” genes (CYBA, LYST, ARPCIB) by full-exome sequencing suggest ambiguity and polymorphism of phenotypic manifestations of complement-mediated mutation.

Outcomes of a patient support programme for subcutaneous immunoglobulin therapy in patients with primary or secondary immunodeficiencies or chronic inflammatory demyelinating polyneuropathy.

Subcutaneous immunoglobulin (SCIg) therapy is important in the treatment of primary (PID) and secondary immunodeficiencies (SID) and chronic inflammatory demyelinating polyneuropathy (CIDP). Patient support programmes (PSPs) help patients self-administer medication regimens and play a more active role in the self-management of their medical conditions. To describe the effectiveness of the CSL Behring CARES PSP in optimising the quality use of SCIg in a hospital-free environment. This retrospective, observational study analysed records of patients enroled in the CSL Behring CARES PSP. Key outcomes were accessibility and effectiveness. Data were extracted from the patient database and analysed using descriptive methods. Seven hundred eighty-nine patients with PID (30.8%), SID (53.4%) and CIDP (15.8%) were enroled in the CARES PSP, 92.8% of whom were referred from public hospitals and the remaining from private hospitals. Of the total patient population, 697 (88.3%) received the nurse-led SCIg self-administration training and education (COACH), out of which 656 (94.1%) completed training and achieved competency after an average of 2.3 training sessions. The proportions of patients who achieved competency were similar across age groups and prior SCIg hospital education status. This is the largest real-world evidence study that describes the effectiveness of SCIg PSPs across three therapeutic disease states. These PSPs can optimise hospital resources such as infusion nurse time and allocation of infusion chairs that were once used for intravenous immunoglobulin infusions, improve patient access to SCIg therapy and enable patients self-administer SCIg outside a hospital environment.

FSCIG 10% in pediatric primary immunodeficiency diseases: a European post-authorization safety study

BackgroundThe safety, tolerability, and immunogenicity of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% (dual-vial unit of human immunoglobulin 10% and recombinant human hyaluronidase [rHuPH20]) were assessed in children with primary immunodeficiency diseases (PIDs).MethodsThis phase 4, post-authorization, prospective, interventional, multicenter study (NCT03116347) conducted in the European Economic Area, enrolled patients aged 2 to < 18 years with a documented PID diagnosis who had received immunoglobulin therapy for ≥ 3 months before enrollment. New fSCIG 10% starters underwent fSCIG 10% dose ramp-up for ≤ 6 weeks (epoch 1) before receiving fSCIG 10% for ≤ 3 years (epoch 2); patients pretreated with fSCIG 10% entered epoch 2 directly. The primary outcome was the number and rate (per infusion) of all noninfectious treatment-related serious and severe adverse events (AEs).ResultsIn total, 42 patients were enrolled and dosed (median [range] age: 11.5 [3–17] years; 81% male; 23 new starters; 19 pretreated). Overall, 49 related noninfectious, treatment-emergent AEs (TEAEs) were reported in 15 patients; most were mild in severity (87.8%). No treatment-related serious TEAEs were reported. Two TEAEs (infusion site pain and emotional distress) were reported as severe and treatment-related in a single new fSCIG 10% starter. The rate of local TEAEs was lower in pretreated patients (0.1 event/patient-year) versus new starters (1.3 events/patient-year). No patients tested positive for binding anti-rHuPH20 antibodies (titer of ≥ 1:160).ConclusionsNo safety signals were identified, and the incidence of local AEs declined over the duration of fSCIG 10% treatment. This study supports fSCIG 10% long-term safety in children with PIDs.Trial registration number (ClinicalTrials.gov)NCT03116347.

Use of Oral Gentamicin in Children with Primary Immunodeficiency and Recurrent Campylobacter coli Bacteremia: A Case Report

Immunosuppressed patients are more at risk of suffering bacteremias due to atypical microorganisms such as Campylobacter coli, which can colonize their intestinal mucosa due to the absence of IgA, the main immunoglobulin of the mucosa and which is not provided with intravenous or subcutaneous immunoglobulin treatment. We have recently had a case of a 5-year-old girl with autosomal recessive agammaglobulinemia with recurrent Campylobacter coli bacteremia and positive stool cultures for the same microorganism. She was treated with intravenous antibiotherapy and given the recurrence of bacteremia, oral gentamicin was associated with this treatment to try to achieve intestinal eradication of the germ. Oral gentamicin was well tolerated, gave no side effects, and managed to eradicate the microorganism 6 months after the end of treatment. We want to reflect the scarce literature on the use of oral gentamicin, the dose and duration of treatment, and the good evolution of our patient with the regimen used.

Acute lung pathology in the immunocompromised child.

Children with compromised immune systems, whether due to primary or secondary immunodeficiencies, are susceptible to a broad spectrum of acute intrathoracic pathologies. These include infections, pulmonary edema, and malignancies. Pulmonary issues are common and perilous in this population, necessitating prompt and precise diagnosis for effective management. This review aims to provide an overview of such conditions, focusing on the imaging appearances of the most prevalent acute lung conditions affecting immunocompromised children. It emphasizes the critical importance of an integrated clinical and radiological approach when diagnosing these acute pulmonary disease states.

COMPARATIVE ANALYSIS OF TREC AND KREC ASSAYS FOR DIAGNOSIS OF PID IN DIFFERENT COUNTRIES

Nationwide neonatal screening programs of lymphocyte production using T-cell recombination excision circles (TREC) and kappa-deleting element recombination circle (KREC) have been important tools for the timely diagnosis of primary immunodeficiency (PID). Diagnosis and treatment of congenital defects of the immune system have made significant strides in many countries. However, a significant part of the children with severe immunodeficiency in the first year of life are diagnosed posthumously. Immunodeficiencies are under diagnosed primarily due to the lack of opportunities for early diagnosis and low awareness of these pathologies in doctors and the other healthcare professionals. Therefore, the issue and importance of early SCID detection using newborn screening assays become an essential public health problem. Newborn screening, particularly through TREC and KREC assays, has emerged as a promising avenue for identifying PID in its nascent stages. Early diagnosis not only facilitates prompt and targeted intervention, but also offers the opportunity to provide improved long-term outcomes for individuals facing these complex disorders. Screening for severe combined immunodeficiency (SCID) was introduced in the Swedish newborn screening program in August 2019, and according to the results from the first year, TREC, KREC and actin beta (ACTB) levels were measured by multiplex qPCR in dried blood spots (DBS) that obtained from 115,786 newborns and children under two years of age. On the basis of low TREC levels, 73 children were requested to undergo further clinical evaluation, resulting in the diagnosis of T-cell lymphopenia in 21 children. The DEPISTREC pilot study in France compared 190,517 infants screened for TREC with a control group of 1,400,000 children. TREC screening identified three patients with SCID, compared to 28 in the control group. Unfortunately, five children in the control group died of SCID before waiting for HSCT, which could potentially have been prevented by TREC screening. An economic analysis showed that the main cost factors were morbidity and cost per test and demonstrated that routine SCID screening was feasible and effective. In addition, two US states, Wisconsin and Massachusetts, have conducted pilot projects funded by the Center for Disease Control to evaluate the feasibility and effectiveness of newborn screening (NBS) for severe combined immunodeficiency (SCID) using the TREC assay. In Wisconsin, 71,000 infants were screened in 2008, identifying eight infants with T-lymphocytopenia, including one successfully treated with cord blood hematopoietic stem cell transplantation (HSCT). In Massachusetts, 100,597 infants were screened in 2009-2010 where twenty-nine infants with T-lymphocytopenia were identified, one of whom had SCID due to a compound heterozygous mutation in JAK3 and also received successful HSCT from an unrelated donor. After successfully identifying T lymphocytopenia in these experiments, the Advisory Committee on Hereditary Diseases of Newborns and Children of the Health and Human Services recommended that SCID be included in a uniform newborn screening panel. Therefore, newborn screening based on TREC and KREC assay programs is expected to provide early detection, prevent infections and prompt treatment, eventually improving overall survival. The ability to detect and intervene in the early stages of immunodeficiency diseases not only improves the prognosis for affected individuals but also enhances our understanding of the prevalence and spectrum of PID in the newborn population.

Impact of the COVID-19 pandemic on Patients with Primary Immunodeficiency

Impact of the COVID-19 pandemic on Patients with Primary Immunodeficiency

Safety and Pharmacokinetics of Nirsevimab in Immunocompromised Children.

Immunocompromised children may have increased risk for severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI), potentially leading to prolonged hospitalization, intensive care, and death. The open-label phase II MUSIC trial evaluated the safety and pharmacokinetics of nirsevimab, an extended half-life monoclonal antibody against RSV, in immunocompromised children aged ≤24 months. Participants received a single intramuscular injection of nirsevimab (first RSV season: 50 mg if <5 kg/100 mg if ≥5 kg; second season: 200 mg). Safety, antidrug antibodies, and pharmacokinetics were evaluated to day 361. Participants (n = 100) had ≥1 immunocompromising conditions: primary immunodeficiency (n = 33), previous transplantation (n = 16), HIV infection (n = 8) or treatment with high-dose systemic corticosteroids (n = 29), immunosuppressive chemotherapy (n = 20), or other immunosuppressive therapies (n = 15). Six children experienced eight treatment-related adverse events (none categorized as serious). Three deaths occurred, all were unrelated to treatment. Eleven children, developed antidrug antibodies, with minimal effects on pharmacokinetics and no apparent impact on safety. Nirsevimab serum concentrations at day 151 were similar to those effective in preventing medically attended RSV LRTI in healthy infants. Fourteen children had increased nirsevimab clearance. No protocol-defined medically attended RSV LRTIs occured through day 151. Among immunocompromised children aged ≤24 months, nirsevimab was well tolerated with no safety concerns and serum concentrations were supportive of efficacy. A subset of children with increased nirsevimab clearance, had conditions potentially associated with protein loss; however, the impact on efficacy is unknown.

Identification and validation of coagulation and fibrinolytic-related diagnostic biomarkers for ulcerative colitis by bioinformatics analysis.

Abnormalities in coagulation and fibrinolytic status have been demonstrated to be relevant to inflammatory bowel disease. Nevertheless, there is no study to methodically examine the role of the coagulation and fibrinolysis-related genes in the diagnosis of ulcerative colitis (UC). UC-related datasets (GSE169568 and GSE94648) were originated from the Gene Expression Omnibus database. The biomarkers related to coagulation and fibrinolysis were identified through combining differentially expressed analysis and machine learning algorithms. Moreover, Gene Set Enrichment Analysis and immune analysis were carried out. A total of 4 biomarkers (MAP2K1, CREBBP, TAF1, and HP) were identified, and biomarkers were markedly enriched in pathways related to immunity, such as T-cell receptor signaling pathway, primary immunodeficiency, chemokine signaling pathway, etc. In total, the infiltrating abundance of 4 immune cells between UC and control was markedly different, namely eosinophils, macrophage M0, resting mast cells, and regulatory T cells. And all biomarkers were significantly relevant to eosinophils. Our findings detected 4 coagulation and fibrinolysis-related biomarkers (MAP2K1, CREBBP, TAF1, and HP) for UC, which contributed to the advancement of UC for further clinical investigation.

Pediatric Plasmablastic Lymphoma in the Setting of CD70 Deficiency.

Combined immunodeficiency due to CD70 deficiency is characterized by increased susceptibility to infections, hypogammaglobulinemia, and malignancy. These patients typically present with chronic Epstein Barr virus (EBV) viremia, severe EBV-related hemophagocytic lymphohistiocytosis, lymphoproliferation, and Hodgkin and non-Hodgkin lymphomas. Plasmablastic lymphoma (PBL) is an extremely rare malignancy in all ages and is predominantly seen in male adults with human immunodeficiency virus infection. EBV infection, immunosuppression, solid organ transplantation, and age-related immune deterioration are also suspected causes of PBL. Nevertheless, there is scarce data about its association with primary immunodeficiencies in the literature. Here, we present the first case of a CD70-deficient pediatric patient with PBL.

Clinical diagnosis of chronic mucocutaneous candidiasis in a patient with recurrent staphylococcal infections

Chronic mucocutaneous candidiasis is a primary immunodeficiency characterized by persistent or recurrent candidal infections of the skin, nails, or mucous membranes. It can be associated with endocrinopathies and autoimmune diseases. A 37-years-old male patient is presented who attended an immunology consultation referred from the dermatology service due to recurrent pyodermitis of several years of evolution; the physical examination also revealed signs of candidiasis in the oral mucosa and lip corners, in the eyelids of both eyes and skin in the abdominal region, which were recurrent, as well as onychomycosis in all toenails. The microbiological study of the pyodermitis lesions showed infection by staphylococcus aureus, and the lesions of the mouth, eyes, abdominal skin and nails showed the presence of Candida albicans. Delayed intradermal skin testing was performed with no T cell response to Candida and Trichophyton antigens. Complementary drugs were indicated to rule out any associated endocrine disorder

Increased Susceptibility of WHIM Mice to Papillomavirus-induced Disease is Dependent upon Immune Cell Dysfunction.

Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome is a rare primary immunodeficiency disease in humans caused by a gain of function in CXCR4, mostly due to inherited heterozygous mutations in CXCR4. One major clinical symptom of WHIM patients is their high susceptibility to human papillomavirus (HPV) induced disease, such as warts. Persistent high risk HPV infections cause 5% of all human cancers, including cervical, anogenital, head and neck and some skin cancers. WHIM mice bearing the same mutation identified in WHIM patients were created to study the underlying causes for the symptoms manifest in patients suffering from the WHIM syndrome. Using murine papillomavirus (MmuPV1) as an infection model in mice for HPV-induced disease, we demonstrate that WHIM mice are more susceptible to MmuPV1-induced warts (papillomas) compared to wild type mice. Namely, the incidence of papillomas is higher in WHIM mice compared to wild type mice when mice are exposed to low doses of MmuPV1. MmuPV1 infection facilitated both myeloid and lymphoid cell mobilization in the blood of wild type mice but not in WHIM mice. Higher incidence and larger size of papillomas in WHIM mice correlated with lower abundance of infiltrating T cells within the papillomas. Finally, we demonstrate that transplantation of bone marrow from wild type mice into WHIM mice normalized the incidence and size of papillomas, consistent with the WHIM mutation in hematopoietic cells contributing to higher susceptibility of WHIM mice to MmuPV1-induced disease. Our results provide evidence that MmuPV1 infection in WHIM mice is a powerful preclinical infectious model to investigate treatment options for alleviating papillomavirus infections in WHIM syndrome.