Aleksandra Matyja-Bednarczyk

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetically determined disorders that lead to immune dysfunction, recurrent infections, and organ-specific complications. The lungs are among the most commonly affected organs, with both infectious and noninfectious manifestations that significantly contribute to morbidity and mortality. This study aimed to provide a comprehensive overview of pulmonary manifestations in IEI, with emphasis on pathophysiological mechanisms, diagnostic approaches, and therapeutic strategies. Methods: A narrative review and synthesis of current literature and clinical guidelines were conducted, focusing on pulmonary involvement in IEI as classified by the International Union of Immunological Societies (IUIS). The analysis included data on infectious and noninfectious complications, imaging findings, immunological assessments, and management strategies, supported by clinical evidence and expert consensus. Results: Pulmonary manifestations in IEI encompass a wide spectrum of conditions. Infectious complications include recurrent bacterial pneumonias, bronchitis, and opportunistic infections, frequently resulting in irreversible lung damage such as bronchiectasis. Noninfectious complications, including granulomatous–lymphocytic interstitial lung disease (GLILD) and interstitial lung disease (ILD), are common in disorders such as common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA). Early diagnosis using high-resolution computed tomography (HRCT) and immunological testing, combined with the timely initiation of immunoglobulin replacement therapy and anti-biotic prophylaxis, significantly improves prognosis. Conclusions: Pulmonary complications are key clinical indicators of IEI and often precede systemic manifestations. Early, integrated, and interdisciplinary diagnostic and therapeutic management are crucial for preventing irreversible lung damage and improving patient outcomes. Regular monitoring and individualized therapy, including immunoglobulin replacement, targeted immunosuppression, and vaccination, are the cornerstones of effective long-term care in IEI.

The SARS-CoV-2 pandemic presents a broad clinical spectrum from asymptomatic cases to severe respiratory failure with high mortality. Severe COVID-19 is characterized by immune dysregulation, including lymphopenia and alterations in the counts of T, B, and NK cells in peripheral blood. Due to the limited data on long-term outcomes related to immune dysregulation, we aimed to analyze immunologic features at baseline in severe and mild COVID-19 cases and assess follow-up characteristics associated with later mortality and long-COVID signs. We included adult patients consecutively hospitalized with COVID-19 between June and November 2020 at the University Hospital in Kraków, corresponding to the first and second waves of COVID-19 in Poland. We enrolled only those who had been thoroughly assessed in terms of clinic and laboratory data, including immunological workups, and survived the acute phase of the disease. In 2025, between February and April (median time of follow-up: 54 months), we conducted a telephone questionnaire on long-COVID symptoms among survivors who had given their consent. Statistical analyses were performed to compare groups with severe and mild disease in terms of dysregulation in lymphocyte subpopulations and the follow-up outcomes. The study included 103 COVID-19 patients, comprising 53 severe (based on the need for at least high-flow nasal oxygen therapy) and 50 mild cases, with no differences in age, sex, and body mass index. Severe COVID-19 patients compared to mild cases had lower CD3+ T cells (count and percentage), CD4+ T cells (count and percentage), CD8+ T cells (count), and NK cells (count), but higher CD19+ B cells (percentage) at baseline (p < 0.05, all). At the time of follow-up, we evaluated 80 patients (77.7% of the baseline participants), with 23 (22.3%) patients lost to follow-up. Among patients analyzed in the follow-up, 23 (28.8%) had died, and 29 of the 57 survivors (50.9%) reported persistent long-COVID symptoms. Patients who died had significantly lower baseline counts of CD3+ T cells (377 vs. 655 cells/µL), CD4+ T cells (224 vs. 372 cells/µL), CD8+ T cells (113 vs. 188 cells/µL), and NK cells (118 vs. 157 cells/µL) compared to survivors (p < 0.05, all). Notably, the percentage of CD19+ B cells was higher in deceased individuals (19.2% vs. 13.5%; p = 0.049). In contrast, we did not document differences in baseline immunological data among survivors with and without long-COVID signs. Our study suggests that dysregulation in lymphocyte subpopulations during the COVID-19 acute phase may be associated with increased late mortality, but not with the persistence of long-COVID symptoms.

Background/Objectives: Inborn errors of immunity (IEI) encompass various congenital disorders, resulting in immunity defects and recurrent infections. Home-based subcutaneous immunoglobulin replacement therapy (scIgRT) is the best treatment option for those with primary antibody deficiency (PAD). However, the lack of standardized procedures in patient training remains a challenge. Our study investigates nurses’ practice and perspectives, aiming to identify areas for improvement in at-home scIgRT practice. Methods: We prepared a structured survey regarding scIgRT, including needle choice experience and perception of adverse events, and distributed it among qualified nurses involved in patient training and scIgRT supervising. Results: We included 56 nurses with a median age of 50 years. Among them, 67.9% represented adult care providers, while 32.1% supervised IgRT in children. Most respondents (83.9%) used the classic or assisted with hyaluronidase scIgRT preparations. Single-channel needles were administered most commonly (85.7%). The needle length was mostly chosen solely by a nurse (57.1%) or in cooperation with the patient (23.2%). Next, 9 mm and 12 mm needles were used most often (92.9% and 78.6%, respectively). As expected, the 6 mm needle was more frequently applied for children compared to adults (n = 16, 88.9% vs. n = 11, 28.9%, p < 0.001), while 12 mm was primarily used in adults (n = 35, 92.1% vs. n = 9, 50.0%, p < 0.001). Visual skin fold assessment was the basis for the needle selection (58.9%), followed by the injection site rule (26.8%) or a choice between two available needle types for thinner or thicker patients (25.0%). Results of this survey indicate that, according to nurses’ opinions presented in this survey, the needle length could be associated with local scIgRT adverse events, such as side needle leakage or local burning. Yet, it was likely unrelated to general adverse signs, such as headaches or dizziness. Most respondents (66.1%) indicated that, even if local adverse events occur, patients are reluctant to change scIgRT preparation or needle length. Most participants (69.6%) reported that the optimal administration technique needs to be discussed with the patient before and during scIgRT. Conclusions: This study sheds light on scIgRT practice in Poland, emphasizing deficiency in needle selection technique. Future research should focus on standardized training and advanced needle selection procedures on patient outcomes, investigating the correlation between needle strategies and adverse events, as well as the effectiveness of scIgRT.

The dynamic development of clinical immunology in Europe began in mid 1980s, and was continued in Poland shortly thereafter. In 1993 the first national consultant in the field of clinical immunology was appointed in Poland. A milestone was the establishment of the Polish Working Group for Primary Immunodeficiencies (PGR for PID) in 2005. Since then, a network of numerous paediatric and internal medicine centres has been created within the Group, facing and resolving new challenges in the field. The study presents the organization of care for patients with primary and secondary immunodeficiencies in Poland, analyzes the staffing situation and patients' access to diagnostics and treatment between late 1980’s and 2024. The summary presents the achievements resulting in improved diagnostic efficiency, shortening the delay in the diagnosis of Inborn Errors of Immunity (IEI)/primary immunodeficiencies (PID), and better access of patients to therapy within drug programs, largely carried out at home. The causes hindering the development of specialization are also analyzed. The most important among them are the lack of systemic support on the part of medical care organizers and the lack of motivation of young doctors to pursue specialization. The main goal is to improve diagnostic and therapeutic procedures for PID patients, including newborn screening, highly specialized, genetic test regardless where they are implemented. It can be only achieved with their better financing. An essential problem is the lack of an epidemiological or clinical IEI registry.

The life expectancy and the risk of developing cardiovascular diseases in patients with inborn errors of immunity are systematically increasing. The aim of the study was to assess cardiovascular risk factors and to evaluate the heart in echocardiography in patients with primary antibody deficiency (PAD). Cardiac echography and selected cardiovascular risk factors, including body mass index, sedentary lifestyle, nicotine, glucose, C-reactive protein, lipid profile, uric acid level, certain chronic diseases, and glucocorticoid use, were analyzed in 94 patients >18 years of age with PAD. Of the patients,25.5% had a cardiovascular disease (mostly hypertension, 18%), 10.5% smoked, 17% were overweight, 14% were obese, and 15% were underweight. Abnormal blood pressure was found in 6.5% of the patients. Lipid metabolism disorders were found in 72.5% of in the studied cohort, increased total cholesterol (45.5%), non-high-density lipoprotein (HDL) (51%), low-density lipoprotein (LDL) (47%), and triglycerides (32%) were observed. Furthermore, 28.5% had a decrease in HDL and 9.5% had a history of hyperuricemia. The average number of risk factors was 5 ± 3 for the entire population and 4 ± 2 for those under 40 years of age. Elevated uric acid levels were found de novo in 4% of participants. In particular, 74.5% of the patients had never undergone an echocardiogram with a successful completion rate of 87% among those tested. Among them, 30% showed parameters within normal limits, primarily regurgitation (92.5%). New pathologies were identified in 28% of patients. Prevention in patients with PAD, aimed at reducing cardiovascular risk, should be a priority. low-density lipoprotein (LDL) (47%), and triglycerides (32%) were observed. Furthermore, 28.5% had a decrease in HDL and 9.5% had a history of hyperuricemia. The average number of risk factors was 5 ± 3 for the entire population and 4 ± 2 for those under 40 years of age. Elevated uric acid levels were found de novo in 4% of participants. In particular, 74.5% of the patients had never undergone an echocardiogram with a successful completion rate of 87% among those tested. Among them, 30% showed parameters within normal limits, primarily regurgitation (92.5%). New pathologies were identified in 28% of patients. Prevention in patients with PAD, aimed at reducing cardiovascular risk, should be a priority.

Recent reports have demonstrated that endothelial injury is critical in the pathogenesis of systemic sclerosis (SSc) and is associated with increased levels of circulating inflammatory biomarkers. This study aims to analyze the serum concentrations of selected cytokines and evaluate their relationship with SSc clinics and the long-term course of the disease. This study included 43 SSc patients and 24 matched healthy controls. In both groups, we measured serum levels of inflammatory cytokines related to the inflammatory response, such as tumor necrosis factor (TNF)α, interferon (IFN)γ, interleukin (IL)-4, IL-6, IL-10, and IL-17, and fibroblast activation protein (FAP). Additionally, in SSc patients, we evaluated the presence of four single nucleotide polymorphisms (SNPs) located in the promotor region of the TNFA gene, namely rs361525, rs1800629, rs1799964, and rs1799724, which might be related to increased TNFα concentrations. The main aim consisted of associating inflammatory cytokines with (1) clinical disease characteristics and (2) longitudinal observation of survival and cancer prevalence. SSc patients were characterized by a 17% increase in serum TNFα. There was no other difference in serum cytokines between the studied groups and diffuse vs. limited SSc patients. As expected, evaluated serum cytokines correlated with inflammatory biomarkers (e.g., IL-6 and C-reactive protein). Interestingly, patients with higher IL-17 had decreased left ventricle ejection fraction. During the median 5-year follow-up, we recorded four cases of neoplastic diseases (lung cancer in two cases, squamous cell carcinoma of unknown origin, and breast cancer with concomitant multiple myeloma) and nine deaths. The causes of death included lung cancer (n = 2), renal crisis (n = 1), multiple-organ failure (n = 1), and unknown reasons in five cases. Surprisingly, higher TNFα was associated with an increased cancer prevalence, while elevated IL-17 with death risk in the follow-up. Furthermore, the AG rs361525 genotype referred to higher TNFα levels than GG carriers. Both AG rs361525 and CT rs1799964 genotypes were associated with increased cancer risk. Higher serum concentrations of TNFα characterize the SSc patients, with the highest values associated with cancer. On the other hand, increased IL-17 in peripheral blood might predict poor SSc prognosis. Further research is needed to validate these findings.

An improved recognition of inborn errors of immunity (IEI) is associated with an increase in life expectancy and a higher incidence of complications and related conditions. The aim of the study was to analyze factors enabling the primary prevention: BMI, smoking and selected laboratory tests (morphology with smear, creatinine, eGFR, total protein, albumin, ferritin, folic acid, vitamin B12, vitamin D3) included in the protocols of standard of care for adult patients with primary antibody deficiencies (PADs). The study included 94 participants ≥ 18 years old, diagnosed with PADs. Overweight was found in 17%, obesity in 14% and underweight in 15% of patients; 11.5% of patients smoked. Leukopenia was diagnosed in 16%, neutropenia in 8.5%, lymphopenia in 22.5% and thrombocytopenia in 14% of patients. A decreased concentration of hemoglobin was found in 32%, total protein in 19%, albumin in 17%, vitamin D3 in 52%, vitamin B12 in 6.5%, folic acid in 34% and ferritin in 26% of patients. Creatinine concentrations were elevated in 16% of patients, while in 20%, eGFR was reduced. Only a holistic assessment of comorbidities and complications of deficiency, as well as regular follow-up and lifestyle changes, can yield the best results in the long-term care of patients.

Data regarding the willingness of patients affected by inborn errors of immunity to accept vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited. Therefore, this study assessed SARS-CoV-2 vaccination coverage and hesitancy in immunodeficient patients by surveying adults with primary immune deficiencies and autoinflammatory and rheumatic diseases on biologic therapy. The study was conducted from September 20, 2021, to January 22, 2022, when the primary coronavirus disease 2019 (COVID-19) vaccinations were available to all adults in Poland. We included 207 participants consecutively recruited from five referral centers (57% female; median age: 42.6 [range: 18–76, standard deviation ± 14.70] years). Overall, 55% (n = 114), 17% (n = 36), and 28% (n = 57) of the patients had primary immune deficiencies, autoinflammatory diseases, and rheumatic diseases, respectively. Among the entire cohort, 168 patients (81%) were vaccinated, and 82% were willing to receive a booster dose. Patients with autoinflammatory diseases had the highest vaccination rate (94.4%). A strong conviction that it was the correct decision (72%), fear of getting COVID-19 (38%), and expert opinions (34%) influenced the decision to vaccinate. Among the unvaccinated patients, 33.3% had primary or vocational education (p <0.001). Furthermore, only 33% believed they were at risk of a severe course of COVID-19 (p = 0.014), and 10% believed in vaccine efficacy (p <0.001). They also doubted the safety of the vaccine (p <0.001) and feared a post-vaccination flare of their disease (p <0.001). Half of the unvaccinated respondents declared that they would consider changing their decision. Vaccination coverage in immunodeficient patients was higher than in the general Polish population. However, the hesitant patients doubted the vaccine’s safety, feared a post-vaccination disease flare, and had primary or vocational education. Therefore, vaccination promotion activities should stress personal safety and the low risk of disease flares due to vaccination. Furthermore, all evidence must be communicated in patient-friendly terms.

The majority of primary immunodeficiencies (PIDs) are antibody deficiencies (PADs), and not all of them are rare diseases; As an example, Caucasian individuals suffer from selective IgA deficiency at a frequency of 1:500.In addition to infections, symptomatic patients with PAD are more likely to develop neoplastic, autoimmune, and allergic diseases. In the event that PAD is neglected or delayed for more than ten years, complications develop, eventually resulting in death. No studies have been conducted to devise and report detailed ready-to-use protocols for managing PAD to date.This study aimed to propose protocols and guidelines for the adult PAD patients’ standard care. Preparing the protocol, we considered the frequency and type of laboratory tests, imaging, endoscopic examinations, specialist consultations, and standardized recommendations for further care in the place of residence. As a result of the proposed monitoring scheme, patients can be provided with complete care in terms of their underlying conditions and comorbidities, as well as early detection of complications. This protocol will serve as a guide for physicians dealing with these patients and enable comparisons of patient groups across a variety of treatment centers, even far away from each other. A national consultant in the field of clinical immunology verified the protocol mainly developed by Polish experts from reference immunology centres for adults.

Tumor necrosis factor (TNF)-α is a proinflammatory cytokine that plays an important role in the pathogenesis of autoimmune diseases. The aim of the study was to establish an association between TNF-α promoter variability and systemic sclerosis (SSc). The study included 43 SSc patients and 74 controls. Four single nucleotide polymorphisms (rs361525, rs1800629, rs1799724, and rs1799964) located at the promoter of the TNFA gene were genotyped using commercially available TaqMan allelic discrimination assays with real-time PCR. The rs1799724 allele was associated with an increased SSc susceptibility (p = 0.028). In turn, none of the polymorphisms studied were related to the clinical and laboratory parameters of SSc patients, except for a higher prevalence of anti-Ro52 antibodies in the AG rs1800629 genotype in comparison to GG carriers (p = 0.04). Three of four cancer patients had both CT rs1799964 and AG rs361525 genotypes; thus, both of them were related to the increased risk of cancer, as compared to the TT (p = 0.03) and GG carriers (p = 0.0003), respectively. The TNFA C rs1799724 variant is associated with an increased risk of SSc, while the CT rs1799964 and AG rs361525 genotypes might enhance cancer susceptibility in SSc patients, although large observational and experimental studies are needed to verify the above hypothesis.