Progressive bronchiectasis and CMC in a patient with STAT1 GOF — a rare case of primary immunodeficiency

Bronchiestasis is a common complication developing in patients with primary immunodeficiency disorders. AD GOF STAT1 defi-ciency is characterized by CMC, repeated infections, and autoimmunity. It is the most frequently diagnosed entity in a group of PIDs with CMC. Here, we present the first Polish case of a female patient with early-onset bronchiestasis accompanied by CMC and a severe course of infections who was genetically diagnosed with AD GOF1 STAT1 mutation at the age of 15

National experience with adenosine deaminase deficiency related SCID in Polish children

IntroductionDeficiency of adenosine deaminase (ADA) manifests as severe combined immunodeficiency (SCID), caused by accumulation of toxic purine degradation by-products. Untreated patients develop immune and non-immune symptoms with fatal clinical course. According to ESID and EBMT recommendations enzyme replacement therapy (ERT) should be implemented as soon as possible to stabilize the patient’s general condition, normalize transaminases, treat pulmonary proteinosis, bone dysplasia, and protect from neurological damage. Hematopoietic stem cell transplantation (HSCT) from a matched related donor (MRD) is a treatment of choice. In absence of such donor, gene therapy (GT) should be considered. HSCT from a matched unrelated donor (MUD) and haploidentical hematopoietic stem cell transplantation (hHSCT) are associated with worse prognosis.Material and methodsWe retrospectively evaluated the clinical course and results of biochemical, immunological and genetic tests of 7 patients diagnosed in Poland with ADA deficiency since 2010 to 2022.ResultsAll patients demonstrated lymphopenia affecting of T, B and NK cells. Diagnosis was made on the basis of ADA activity in red blood cells and/or genetic testing. Patients manifested with various non-immunological symptoms including: lung proteinosis, skeletal dysplasia, liver dysfunction, atypical hemolytic-uremic syndrome, and psychomotor development disorders. Five patients underwent successful HSCT: 3 patients from matched unrelated donor, 2 from matched sibling donor, and 1 haploidentical from a parental donor. In 4 patients HSCT was preceded by enzyme therapy (lasting from 2 to 5 months). One patient with multiple organ failure died shortly after admission, before the diagnosis was confirmed. None of the patients had undergone gene therapy.ConclusionsIt is important to diagnose ADA SCID as early as possible, before irreversible multi-organ failure occurs. In Poland HSCT are performed according to international immunological societies recommendations, while ERT and GT are less accessible. Implementation of Newborn Screening (NBS) for SCID in Poland could enable recognition of SCID, including ADA-SCID

Periodic fever syndromes in Eastern and Central European countries: results of a pediatric multinational survey

<p>Abstract</p> <p>Objective</p> <p>To analyze the prevalence of diagnosed and suspected autoinflammatory diseases in Eastern and Central European (ECE) countries, with a particular interest on the diagnostic facilities in these countries.</p> <p>Methods</p> <p>Two different strategies were used to collect data on patients with periodic fever syndromes from ECE countries- the Eurofever survey and collection of data with the structured questionnaire.</p> <p>Results</p> <p>Data from 35 centers in 14 ECE countries were collected. All together there were 11 patients reported with genetically confirmed familial Mediterranean fever (FMF), 14 with mevalonate-kinase deficiency (MKD), 11 with tumor necrosis factor receptor associated periodic syndrome (TRAPS) and 4 with chronic infantile neurological cutaneous and articular syndrome (CINCA). Significantly higher numbers were reported for suspected cases which were not genetically tested. All together there were 49 suspected FMF patients reported, 24 MKD, 16 TRAPS, 7 CINCA and 2 suspected Muckle-Wells syndrome (MWS) patients.</p> <p>Conclusions</p> <p>The number of genetically confirmed patients with periodic fever syndromes in ECE countries is very low. In order to identify more patients in the future, it is important to organize educational programs for increasing the knowledge on these diseases and to establish a network for genetic testing of periodic fever syndromes in ECE countries.</p

Progressive Bronchiectasis and CMC in a Patient with STAT1 GOF—A Rare Case of Primary Immunodeficiency

Bronchiestasis is a common complication developing in patients with primary immunodeficiency disorders. AD GOF STAT1 defi-ciency is characterized by CMC, repeated infections, and autoimmunity. It is the most frequently diagnosed entity in a group of PIDs with CMC. Here, we present the first Polish case of a female patient with early-onset bronchiestasis accompanied by CMC and a severe course of infections who was genetically diagnosed with AD GOF1 STAT1 mutation at the age of 15

EuroFlow standardized approach to diagnostic immunopheneotyping of severe PID in newborns and young children

The EuroFlow PID consortium developed a set of flow cytometry tests for evaluation of patients with suspicion of primary immunodeficiency (PID). In this technical report we evaluate the performance of the SCID-RTE tube that explores the presence of recent thymic emigrants (RTE) together with T-cell activation status and maturation stages and discuss its applicability in the context of the broader EuroFlow PID flow cytometry testing algorithm for diagnostic orientation of PID of the lymphoid system. We have analyzed peripheral blood cells of 26 patients diagnosed between birth and 2 years of age with a genetically defined primary immunodeficiency disorder: 15 severe combined immunodeficiency (SCID) patients had disease-causing mutations in RAG1 or RAG2 (n = 4, two of them presented with Omenn syndrome), IL2RG (n = 4, one of them with confirmed maternal engraftment), NHEJ1 (n = 1), CD3E (n = 1), ADA (n = 1), JAK3 (n = 3, two of them with maternal engraftment) and DCLRE1C (n = 1) and 11 other PID patients had diverse molecular defects [ZAP70 (n = 1), WAS (n = 2), PNP (n = 1), FOXP3 (n = 1), del22q11.2 (DiGeorge n = 4), CDC42 (n = 1) and FAS (n = 1)]. In addition, 44 healthy controls in the same age group were analyzed using the SCID-RTE tube in four EuroFlow laboratories using a standardized 8-color approach. RTE were defined as CD62L+CD45RO-HLA-DR-CD31+ and the activation status was assessed by the expression of HLA-DR+. Naïve CD8+ T-lymphocytes and naïve CD4+ T-lymphocytes were defined as CD62L+CD45RO-HLA-DR-. With the SCID-RTE tube, we identified patients with PID by low levels or absence of RTE in comparison to controls as well as low levels of naïve CD4+ and naïve CD8+ lymphocytes. These parameters yielded 100% sensitivity for SCID. All SCID patients had absence of RTE, including the patients with confirmed maternal engraftment or oligoclonally expanded T-cells characteristic for Omenn syndrome. Another dominant finding was the increased numbers of activated CD4+HLA-DR+ and CD8+HLA-DR+ lymphocytes. Therefore, the EuroFlow SCID-RTE tube together with the previously published PIDOT tube form a sensitive and complete cytometric diagnostic test suitable for patients suspected of severe PID (SCID or CID) as well as for children identified via newborn screening programs for SCID with low or absent T-cell receptor excision circles (TRECs).MBa was supported by Grant Agency of the Charles university (GAUK 316218); MBl by ZonMW project 543002002 (SONNET study); VK by project NV19-05-00332 from Ministry of Health, and TK by project LO1604 from Ministry of Education, Youth and Sports Czech Republic and cytometer instrument was supported by EU-Prague project CZ.2.16/3.1.00/24505. MP-A was supported by a grant from Fundación Mutua Madrileña (Madrid, Spain). The EuroFlow Consortium received support from the FP6-2004-LIFESCIHEALTH-5 program of the European Commission (grant LSHB-CT-2006-018708) as Specific Targeted Research Project (STREP).Peer reviewe

COVID-19 in unvaccinated patients with inborn errors of immunity - Polish experience

At the beginning of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, patients with inborn errors of immunity (IEI) appeared to be particularly vulnerable to a severe course of the disease. It quickly turned out that only some IEI groups are associated with a high risk of severe infection. However, data on the course of Coronavirus Disease 2019 (COVID-19) in patients with IEI are still insufficient, especially in children; hence, further analyses are required. The retrospective study included 155 unvaccinated people with IEI: 105 children and 50 adults (67.7% and 32.3%, respectively). Male patients dominated in the study group (94 people, 60.6%). At least two comorbidities were found in 50 patients (32.3%), significantly more often in adults (56% vs. 21%). Adult patients presented significantly more COVID-19 symptoms. Asymptomatic and mildly symptomatic course of COVID-19 was demonstrated in 74.8% of the entire group, significantly more often in children (88.6% vs. 46%). Moderate and severe courses dominated in adults (54% vs. 11.4%). Systemic antibiotic therapy was used the most frequently, especially in adults (60% vs. 14.3%). COVID-19-specific therapy was used almost exclusively in adults. In the whole group, complications occurred in 14.2% of patients, significantly more often in adults (30% vs. 6.7%). In the pediatric group, there were two cases (1.9%) of multisystem inflammatory syndrome in children. Deaths were reported only in the adult population and accounted for 3.9% of the entire study group. The death rate for all adults was 12%, 15.4% for adults diagnosed with common variable immunodeficiency, 12.5% for those with X-linked agammaglobulinemia, and 21.4% for patients with comorbidity. The results of our study imply that vaccinations against COVID-19 should be recommended both for children and adults with IEI. Postexposure prophylaxis and early antiviral and anti-SARS-CoV-2 antibody-based therapies should be considered in adults with IEI, especially in those with severe humoral immune deficiencies and comorbidity