RARE DISEASE
Primary immunodeficiency
Primary immunodeficiency
Primary immunodeficiency
Drug discovery
1
drug
With orphan designation
Overview
Primary immunodeficiency (PI) encompasses over 450 genetic disorders impairing immune function, increasing susceptibility to infections, autoimmunity, and malignancy [1][6][18]. Diagnosis is often delayed due to variable presentations, leading to complications like organ damage and lymphoproliferative disorders [1][14]. Management involves infection prevention, immune modulation, and targeted therapies [3][6][8].
Burden
Recurrent infections drive chronic lung damage, hearing loss, and hospitalizations, with 63% of patients requiring inpatient care [6][7][11].
22-30% develop autoimmune or lymphoproliferative complications [1][6].
Delayed diagnosis (9-15 years) amplifies morbidity and healthcare costs, with 70% of cases undiagnosed [14][19].
Therapies
Immunoglobulin replacement (IV/SC) for antibody deficiencies, used in 42.9% of patients with B-cell defects [6][8][16].
Antimicrobial prophylaxis (antibiotics, antifungals) tailored to immune defect profiles [3][16].
Curative approaches: Hematopoietic stem cell transplantation for severe cases (e.g., SCID) and emerging gene therapies targeting specific mutations [3][8][16].
Categories: rare genetic diseases, rare immunological diseases
Research Papers
2,127 drug discovery papers about Primary immunodeficiency, with 5 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,127 drug discovery papers about Primary immunodeficiency, with 5 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-07 | Safety and tolerability of a new intravenous immunoglobulin 10% in patients with primary immunodeficiency.
Kedrion IVIg 10% (KIg10; QIVIGY) is a new, ready-to-use, 10% liquid IVIg (100 mg/mL) approved for adults with primary immunodeficiency (PI). This report presents safety and tolerability data from a phase III study. This was an open-label, prospective, single-arm, historically controlled, multicenter study in adults with confirmed PI receiving commercially available IVIg products. Participants received KIg10 200-800 mg/kg once every 21 or 28 days for 17 and 13 infusions, respectively. Forty-seven participants received KIg10 every 21 days (n = 8) or every 28 days (n = 39). Overall, 97.9% (n = 46) of participants had treatment-emergent adverse events (TEAEs) and 46.8% (n = 22) experienced drug-related TEAEs; most were mild or moderate. Across 80 infusions, 122 infusional AEs occurred in 30 participants (63.8%); infusional AEs decreased with later versus initial infusions. No life-threatening TEAEs, deaths, serious or severe drug-related TEAEs, thrombotic events, or occurrences of aseptic meningitis, transfusion-related acute lung injury, acute renal failure, or neutropenia were observed. A drug-related hypersensitivity event (skin reaction) occurred in 1 participant. Forty-four (93.6%) participants reached the maximum dose rate (8 mg/kg/min). KIg10 was well tolerated in adults with PI, supporting its use as a replacement therapy option in this population.
2026-07-28 | Evolution of Inborn Errors of Immunity in China: Discoveries and Treatment Paradigms.
Inborn errors of immunity (IEI) are monogenic disorders of the immune system that lead to immunodeficiency, autoimmunity, autoinflammation, allergy, and/or cancer. This review provides a comparative review of the epidemiology, clinical manifestations, and management of IEI in China. While individual forms of IEI are generally rare disorders globally, collectively they represent a significant disease burden. China has recently made great strides in the diagnosis and treatment of IEIs with the increasing utility of next-generation sequencing and the availability of hematopoietic stem cell transplantation. Challenges remain in the establishment of national registry databases comparable to the European Society for Immunodeficiencies and The United States Immunodeficiency Network. Also, the absence of a national newborn screening program for severe combined immunodeficiency poses risks regarding live attenuated vaccination in undiagnosed infants. Current access to treatment including subcutaneous immunoglobulin, targeted molecular therapies, and commercialized gene therapy remains limited in China. Nevertheless, the therapeutic landscape is rapidly evolving, marked by an increasing clinical application of precision molecular-targeted treatments and the emergence of AI-empowered gene editing therapies. Ultimately, advancing the field of IEI necessitates global collaboration, integrating the complementary strengths of both regions to establish scientific breakthroughs and clinical innovation.
2026-07-15 | Bronchiectasis With Inborn Errors of Immunity: Zooming in on Predominantly Antibody Deficiencies.
Bronchiectasis is a chronic inflammatory lung disease characterized by permanent airway dilation, mucus production, recurrent infections, and progressive structural injury. Inborn errors of immunity (IEIs), particularly predominantly antibody deficiencies (PADs), are important and potentially under-recognized causes of non-cystic fibrosis bronchiectasis (NCFB). Antibody deficiency increases susceptibility to bacterial infection, but the observation that bronchiectasis develops in only a subset of patients with PADs, and may develop despite immunoglobulin replacement therapy (IGRT), indicates that serum antibody measurements alone do not fully define the airway risk. Bronchiectasis in IEI likely reflects the interaction of impaired systemic humoral immunity impacting mucosal immune defenses, altered IgG transport or catabolism, B-cell dysregulation, T-cell and innate immune dysfunction, autoimmunity, environmental exposures, comorbid lung disease, and chronic airway infection. In this review, we summarize reported frequencies of NCFB among selected IEIs with antibody deficiency, discuss the limitations of IgG subclass and serum-based antibody testing as predictors of airway disease, and review evidence supporting higher individualized IGRT dosing in patients with antibody deficiency and bronchiectasis to achieve therapeutic IgG levels. We also propose a practical clinical framework for evaluating immune defects in bronchiectasis and for longitudinal pulmonary screening in patients with IEIs at increased risk of bronchiectasis.
2026-07-15 | A scientometric analysis of research related to the 'oral-placental axis' hypothesis: current status, hotspots, and future directions.
Oral diseases and placental disorders are closely associated with adverse pregnancy outcomes, and accumulating evidence supports their crosstalk that constitutes the "oral-placental axis". This study integrated scientometric and bioinformatic approaches to systematically analyze global research trends, collaboration networks, research hotspots, and core molecular-microbial mechanisms of the oral-placental axis covering the period from 2016 to 2025. A total of 196 eligible publications were retrieved from the Web of Science Core Collection, Scopus, and PubMed. Bibliometric visualization was performed using VOSviewer, CiteSpace, and R-bibliometrix, and bioinformatic analysis was conducted to identify shared genes, signaling pathways, and microbial links between oral and placental diseases. The results revealed an annual publication growth rate of 5.03%, with the United States, China, and Australia as major contributing countries, the University of Queensland as the leading institution, and Gomez-Arango Luisa F. and Nitert Marloes Dekker as the most influential authors. Core keywords included preterm birth, periodontal diseases, gestational diabetes mellitus, and oral microbiome, reflecting a research shift from phenotypic association to mechanistic exploration such as microbial vertical transmission and inflammatory signaling. Mechanistic analyses identified shared hub genes (e.g., KRT19, ADAMDEC1, AQP9, SPAG4, PLAT) and key pathways, predominantly primary immunodeficiency and complement and coagulation cascades. Pathogenic bacteria including Fusobacterium nucleatum and Porphyromonas gingivalis mediated adverse pregnancy outcomes via hematogenous spread and placental barrier disruption. This study established a bidirectional regulatory model of the oral-placental axis involving shared risks, microbial transmission, and systemic inflammation, providing a theoretical basis for preconception oral intervention and precise prevention during pregnancy, and supporting the integration of oral care into routine perinatal management.
2026-07-11 | Evaluation of sleep, fatigue, and quality of life in patients with primary immunodeficiency.
Primary immunodeficiency (PID) is a heterogeneous group of genetic disorders characterized by recurrent infections and immune dysregulation. Despite advances in therapy, many patients experience impaired quality of life (QoL), fatigue, and sleep disturbances. This study aimed to evaluate sleep quality, fatigue, and health-related QoL in adults with PID and to explore the associations between comorbidities and treatment modalities. This retrospective, observational, single-center study was conducted at the University of Health Sciences, Gülhane Training and Research Hospital between May and August 2024. Forty-nine adult patients with PID, diagnosed according to international criteria, completed validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), and SF-36 QoL scale. Clinical and demographic data were retrieved from the medical records. Statistical analyses included t-tests, Mann-Whitney U, chi-square, and Pearson's correlation, with significance set at P < 0.05. Of 49 patients (55.1% males, mean follow-up 9.9 years), 36.7% had poor sleep quality, 42.9% reported severe fatigue, 49% showed impaired SF-36 physical scores, and 87.8% had preserved mental scores. Poor sleep quality was correlated positively with fatigue (r = 0.623, P < 0.001) and negatively correlated with physical QoL (r = -0.491, P < 0.001). Patients with autoimmune and inflammatory bowel disease had significantly worse PSQI and FSS scores, whereas bronchiectasis was associated with reduced SF-36 physical scores. No differences were observed between the IVIG and SCIG groups in fatigue or mental scores; however, SCIG recipients had significantly higher physical scores (P = 0.018). Patients with PID experience substantial impairment in physical QoL, with fatigue and poor sleep quality frequently coexisting. Comorbidities, such as autoimmunity, bronchiectasis, and inflammatory bowel disease, exacerbate these impairments. SCIG therapy confers better physical outcomes than IVIG therapy. Comprehensive care strategies that address psychosocial and physical health are essential for the management of PID.
2026-08-07 | Safety and tolerability of a new intravenous immunoglobulin 10% in patients with primary immunodeficiency.
Kedrion IVIg 10% (KIg10; QIVIGY) is a new, ready-to-use, 10% liquid IVIg (100 mg/mL) approved for adults with primary immunodeficiency (PI). This report presents safety and tolerability data from a phase III study. This was an open-label, prospective, single-arm, historically controlled, multicenter study in adults with confirmed PI receiving commercially available IVIg products. Participants received KIg10 200-800 mg/kg once every 21 or 28 days for 17 and 13 infusions, respectively. Forty-seven participants received KIg10 every 21 days (n = 8) or every 28 days (n = 39). Overall, 97.9% (n = 46) of participants had treatment-emergent adverse events (TEAEs) and 46.8% (n = 22) experienced drug-related TEAEs; most were mild or moderate. Across 80 infusions, 122 infusional AEs occurred in 30 participants (63.8%); infusional AEs decreased with later versus initial infusions. No life-threatening TEAEs, deaths, serious or severe drug-related TEAEs, thrombotic events, or occurrences of aseptic meningitis, transfusion-related acute lung injury, acute renal failure, or neutropenia were observed. A drug-related hypersensitivity event (skin reaction) occurred in 1 participant. Forty-four (93.6%) participants reached the maximum dose rate (8 mg/kg/min). KIg10 was well tolerated in adults with PI, supporting its use as a replacement therapy option in this population.
2026-07-28 | Evolution of Inborn Errors of Immunity in China: Discoveries and Treatment Paradigms.
Inborn errors of immunity (IEI) are monogenic disorders of the immune system that lead to immunodeficiency, autoimmunity, autoinflammation, allergy, and/or cancer. This review provides a comparative review of the epidemiology, clinical manifestations, and management of IEI in China. While individual forms of IEI are generally rare disorders globally, collectively they represent a significant disease burden. China has recently made great strides in the diagnosis and treatment of IEIs with the increasing utility of next-generation sequencing and the availability of hematopoietic stem cell transplantation. Challenges remain in the establishment of national registry databases comparable to the European Society for Immunodeficiencies and The United States Immunodeficiency Network. Also, the absence of a national newborn screening program for severe combined immunodeficiency poses risks regarding live attenuated vaccination in undiagnosed infants. Current access to treatment including subcutaneous immunoglobulin, targeted molecular therapies, and commercialized gene therapy remains limited in China. Nevertheless, the therapeutic landscape is rapidly evolving, marked by an increasing clinical application of precision molecular-targeted treatments and the emergence of AI-empowered gene editing therapies. Ultimately, advancing the field of IEI necessitates global collaboration, integrating the complementary strengths of both regions to establish scientific breakthroughs and clinical innovation.
2026-07-15 | Bronchiectasis With Inborn Errors of Immunity: Zooming in on Predominantly Antibody Deficiencies.
Bronchiectasis is a chronic inflammatory lung disease characterized by permanent airway dilation, mucus production, recurrent infections, and progressive structural injury. Inborn errors of immunity (IEIs), particularly predominantly antibody deficiencies (PADs), are important and potentially under-recognized causes of non-cystic fibrosis bronchiectasis (NCFB). Antibody deficiency increases susceptibility to bacterial infection, but the observation that bronchiectasis develops in only a subset of patients with PADs, and may develop despite immunoglobulin replacement therapy (IGRT), indicates that serum antibody measurements alone do not fully define the airway risk. Bronchiectasis in IEI likely reflects the interaction of impaired systemic humoral immunity impacting mucosal immune defenses, altered IgG transport or catabolism, B-cell dysregulation, T-cell and innate immune dysfunction, autoimmunity, environmental exposures, comorbid lung disease, and chronic airway infection. In this review, we summarize reported frequencies of NCFB among selected IEIs with antibody deficiency, discuss the limitations of IgG subclass and serum-based antibody testing as predictors of airway disease, and review evidence supporting higher individualized IGRT dosing in patients with antibody deficiency and bronchiectasis to achieve therapeutic IgG levels. We also propose a practical clinical framework for evaluating immune defects in bronchiectasis and for longitudinal pulmonary screening in patients with IEIs at increased risk of bronchiectasis.
2026-07-15 | A scientometric analysis of research related to the 'oral-placental axis' hypothesis: current status, hotspots, and future directions.
Oral diseases and placental disorders are closely associated with adverse pregnancy outcomes, and accumulating evidence supports their crosstalk that constitutes the "oral-placental axis". This study integrated scientometric and bioinformatic approaches to systematically analyze global research trends, collaboration networks, research hotspots, and core molecular-microbial mechanisms of the oral-placental axis covering the period from 2016 to 2025. A total of 196 eligible publications were retrieved from the Web of Science Core Collection, Scopus, and PubMed. Bibliometric visualization was performed using VOSviewer, CiteSpace, and R-bibliometrix, and bioinformatic analysis was conducted to identify shared genes, signaling pathways, and microbial links between oral and placental diseases. The results revealed an annual publication growth rate of 5.03%, with the United States, China, and Australia as major contributing countries, the University of Queensland as the leading institution, and Gomez-Arango Luisa F. and Nitert Marloes Dekker as the most influential authors. Core keywords included preterm birth, periodontal diseases, gestational diabetes mellitus, and oral microbiome, reflecting a research shift from phenotypic association to mechanistic exploration such as microbial vertical transmission and inflammatory signaling. Mechanistic analyses identified shared hub genes (e.g., KRT19, ADAMDEC1, AQP9, SPAG4, PLAT) and key pathways, predominantly primary immunodeficiency and complement and coagulation cascades. Pathogenic bacteria including Fusobacterium nucleatum and Porphyromonas gingivalis mediated adverse pregnancy outcomes via hematogenous spread and placental barrier disruption. This study established a bidirectional regulatory model of the oral-placental axis involving shared risks, microbial transmission, and systemic inflammation, providing a theoretical basis for preconception oral intervention and precise prevention during pregnancy, and supporting the integration of oral care into routine perinatal management.
2026-07-11 | Evaluation of sleep, fatigue, and quality of life in patients with primary immunodeficiency.
Primary immunodeficiency (PID) is a heterogeneous group of genetic disorders characterized by recurrent infections and immune dysregulation. Despite advances in therapy, many patients experience impaired quality of life (QoL), fatigue, and sleep disturbances. This study aimed to evaluate sleep quality, fatigue, and health-related QoL in adults with PID and to explore the associations between comorbidities and treatment modalities. This retrospective, observational, single-center study was conducted at the University of Health Sciences, Gülhane Training and Research Hospital between May and August 2024. Forty-nine adult patients with PID, diagnosed according to international criteria, completed validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), and SF-36 QoL scale. Clinical and demographic data were retrieved from the medical records. Statistical analyses included t-tests, Mann-Whitney U, chi-square, and Pearson's correlation, with significance set at P < 0.05. Of 49 patients (55.1% males, mean follow-up 9.9 years), 36.7% had poor sleep quality, 42.9% reported severe fatigue, 49% showed impaired SF-36 physical scores, and 87.8% had preserved mental scores. Poor sleep quality was correlated positively with fatigue (r = 0.623, P < 0.001) and negatively correlated with physical QoL (r = -0.491, P < 0.001). Patients with autoimmune and inflammatory bowel disease had significantly worse PSQI and FSS scores, whereas bronchiectasis was associated with reduced SF-36 physical scores. No differences were observed between the IVIG and SCIG groups in fatigue or mental scores; however, SCIG recipients had significantly higher physical scores (P = 0.018). Patients with PID experience substantial impairment in physical QoL, with fatigue and poor sleep quality frequently coexisting. Comorbidities, such as autoimmunity, bronchiectasis, and inflammatory bowel disease, exacerbate these impairments. SCIG therapy confers better physical outcomes than IVIG therapy. Comprehensive care strategies that address psychosocial and physical health are essential for the management of PID.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Primary immunodeficiency.
1 orphan drug designation for Primary immunodeficiency.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Immune Globulin Subcutaneous (Human) | proteins | FDA | 2004-09-22 | — | CSL Behring |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI's forecasts to outperform average preclinical success rates. Whether you're expanding your R&D pipeline, evaluating a partnership, or simply have a question — we'd love to hear from you.