A Report on the Clinical Efficacy of Rituximab Administration in Patients with Inborn Errors of Immunity and Autoimmune/Autoinflammatory Manifestations
-
Samin Sharafian
,
Mahya Mohammadi
,
Samin Alavi
,
Mehrnaz Mesdaghi
,
Reza Shiari
,
Bibi Shahin Shamsian
,
Peyman Eshghi
,
Hedieh Haji Khodaverdi Khani
,
Hassan Abolghasemi
,
Abdollah Karimi
,
Nasrin Behniafard
,
Parastoo Mollaei Tavana
,
Mohammad Mehdi Nasehi
,
Mozhgan Hashemieh
,
Mehran Khodashenas
,
Mahnaz Jamee
,
Zahra Chavoshzadeh
,
Narges Eslami
Abstract
It can sometimes be very difficult to control the manifestations of autoimmunity and lymphoproliferation in patients with primary immunodeficiency diseases, and there is no adequate response to first-line treatments. Rituximab (RTX), as a second-line treatment, is efficacious and well-tolerated for the management of these clinical manifestations.
This retrospective study was conducted to analyze the clinical, immunological, and genetic findings together with the response rate to RTX therapy in subjects with inborn errors of immunity (IEI) and autoimmune or autoinflammatory manifestations. In this study, 23 individuals with IEI and autoimmune or lymphoproliferation manifestations who received RTX between April 2008 and 2021 were evaluated.
Fifteen out of the 23 patients were female. The median age of cases was 12 years. The moderate and severe adverse reactions, including fever, diarrhea, and anaphylaxis shock, were manifested during RTX infusion in 5 patients. In total, 86.9% of patients responded to rituximab (complete response: n=14, partial response: n=6) while three failed to respond. The median response time to RTX treatment was 50 days. All patients were given monthly intravenous immunoglobulin (IVIG) therapy. Pneumonia and candidiasis occurred in one patient a week after receiving the second injection of RTX. Eight patients expired during follow-up.
In conclusion, the response rate of RTX could be improved through administering monthly IVIG for hypogammaglobulinemia treatment following RTX infusion. Early use of rituximab leads to a better response rate in comparison with late use of rituximab in multitreated refractory patients. The efficient cumulative dose of rituximab remains undefined.
1. Tiri A, Masetti R, Conti F, Tignanelli A, Turrini E, Bertolini P, et al. Inborn Errors of Immunity and Cancer. Biology. 2021;10(4).
2. Notarangelo LD, Bacchetta R, Casanova JL, Su HC. Human inborn errors of immunity: An expanding universe. Sci Immunol. 2020;5(49).
3. Fischer A, Provot J, Jais JP, Alcais A, Mahlaoui N. Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies. J Allergy Clin Immunology. 2017;140(5):1388-93.e8.
4. Leiding JW, Forbes LR. Mechanism-Based Precision Therapy for the Treatment of Primary Immunodeficiency and Primary Immunodysregulatory Diseases. J Allergy Clin Immunol Practice. 2019;7(3):761-73.
5. Barmettler S, Ong MS, Farmer JR, Choi H, Walter
J. Association of Immunoglobulin Levels, Infectious
Risk, and Mortality With Rituximab and Hypogammaglobulinemia. JAMA. 2018;1(7):e184169.
6. Kaplan B, Kopyltsova Y, Khokhar A, Lam F, Bonagura V. Rituximab and immune deficiency: case series and review of the literature. J Allergy Clin Immunol Practice. 2014;2(5):594-600.
7. Pecoraro A, Crescenzi L, Galdiero MR, Marone G, Rivellese F, Rossi FW, et al. Immunosuppressive therapy with rituximab in common variable immunodeficiency. Clin Mol Allergy. 2019;17:9.
8. Azizi G, Ziaee V, Tavakol M, Alinia T, Yazdai R, Mohammadi H, et al. Approach to the Management of Autoimmunity in Primary Immunodeficiency. Scand J Immunol. 2017;85(1):13-29.
9. Food, Administration D. Highlights of Prescribing Information (Rituxan).
10. Kasi PM, Tawbi HA, Oddis CV, Kulkarni HS. Clinical review: Serious adverse events associated with the use of rituximab - a critical care perspective. Critical care. 2012;16(4):231.
11. Zian Z, Berry SPD, Bahmaie N, Ghotbi D, Kashif A, Madkaikar M, et al. The clinical efficacy of Rituximab administration in autoimmunity disorders, primary immunodeficiency diseases and malignancies. Int Immunopharmacol. 2021;95:107565.
12. Seidel MG, Kindle G, Gathmann B, Quinti I, Buckland M, van Montfrans J, et al. The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity. The journal of allergy and clinical immunology In practice. 2019;7(6):1763-70.
13. Amaya-Uribe L, Rojas M, Azizi G, Anaya JM, Gershwin ME. Primary immunodeficiency and autoimmunity: A comprehensive review. J Autoimmunity. 2019;99:52-72.
14. Bardou MLD, Henriques MT, Grumach AS. Inborn errors of immunity associated with characteristic phenotypes. Jornal de pediatria. 2021;97 Suppl 1(Suppl 1):S75-s83.
15. Bousfiha A, Jeddane L, Picard C, Al-Herz W, Ailal F, Chatila T, et al. Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification. J Clin Immunol. 2020;40(1):66-81.
16. Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood advances. 2019;3(23):3829-66.
17. Program CTE. Common terminology criteria for adverse events (CTCAE). v. 5.0 [5x7]. Cancer ther Eval Progr. 2017.
18. Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386-93.
19. McLaughlin P, Grillo-López AJ, Link BK, Levy R, Czuczman MS, Williams ME, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Cin Oncol. 1998;16(8):2825-33.
20. England N. Clinical commissioning policy statement: biologic therapies for the treatment of juvenile idiopathic arthritis (JIA). 2015. Contract No: NHS England E03X04 E.3.
21. Herrero-Morant A, Álvarez-Reguera C, Martín-Varillas JL, Calvo-Río V, Casado A, Prieto-Peña D, et al. Biologic Therapy in Refractory Non-Multiple Sclerosis Optic Neuritis Isolated or Associated to Immune-Mediated Inflammatory Diseases. A Multicenter Study. J Clin Med. 2020;9(8).
22. Marciano BE, Holland SM. Primary Immunodeficiency Diseases: Current and Emerging Therapeutics. Front Immunol. 2017;8:937.
23. Zecca M, De Stefano P, Nobili B, Locatelli F. Anti-CD20 monoclonal antibody for the treatment of severe, immune-mediated, pure red cell aplasia and hemolytic anemia. Blood. 2001;97(12):3995-7.
24. Rao A, Kelly M, Musselman M, Ramadas J, Wilson D, Grossman W, et al. Safety, efficacy, and immune reconstitution after rituximab therapy in pediatric patients with chronic or refractory hematologic autoimmune cytopenias. Pediatric Blood Cancer. 2008;50(4):822-5.
25. Wang J, Wiley JM, Luddy R, Greenberg J, Feuerstein MA, Bussel JB. Chronic immune thrombocytopenic purpura in children: assessment of rituximab treatment. J Pediatrics. 2005;146(2):217-21.
26. Serris A, Amoura Z, Canouï-Poitrine F, Terrier B, Hachulla E, Costedoat-Chalumeau N, et al. Efficacy and safety of rituximab for systemic lupus erythematosus-associated immune cytopenias: A multicenter retrospective cohort study of 71 adults. Ame J Hematol. 2018;93(3):424-9.
27. Zecca M, Nobili B, Ramenghi U, Perrotta S, Amendola G, Rosito P, et al. Rituximab for the treatment of refractory autoimmune hemolytic anemia in children. Blood. 2003;101(10):3857-61.
28. Ajmi H, Mabrouk S, Hassayoun S, Regaieg H, Tfifha M, Jalel C, et al. Success of anti-CD20 monoclonal antibody treatment for severe autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, and immunoglobulin M autoantibodies in a child: a case report. J Med Case Rep. 2017;11(1):321.
29. Ansari S, Tashvighi M, Darbandi B, Salimi AB, Golpaygani M. Rituximab for child with chronic relapsing autoimmune hemolytic anemia. Pediatric Hematol Oncol. 2011;28(2):164-6.
30. Dev M, Mushtaq N, Faisal A. A case of autoimmune haemolytic anaemia achieving complete response with rituximab. J Pak Med Assoc. 2014;64(6):700-2.
31. Gottardo NG, Baker DL, Willis FR. Successful induction and maintenance of long-term remission in a child with chronic relapsing autoimmune hemolytic anemia using rituximab. Pediatr Hematol Oncol. 2003;20(7):557-61.
32. Kuzmanovic M, Jurisic V. Rituximab for treatment of autoimmune hemolytic anemia. Indian pediatr. 2012;49(8):672-4.
33. Makadia D, Siddaiahgari SR, Latha MS. Anti B cell targeted therapy for autoimmune hemolytic anemia in an infant. Indian J Pharmacol. 2013;45(5):526-7.
34. Moriya K, Matsuhashi T, Onuma M, Niizuma H, Rikiishi T, Asada H, et al. Successful treatment with rituximab of an infant with refractory autoimmune hemolytic anemia. Int J Hematol. 2013;98(2):237-9.
35. Quartier P, Brethon B, Philippet P, Landman-Parker J, Le Deist F, Fischer A. Treatment of childhood autoimmune haemolytic anaemia with rituximab. Lancet. 2001;358(9292):1511-3.
36. Wakim M, Shah A, Arndt PA, Garratty G, Weinberg K, Hofstra T, et al. Successful anti-CD20 monoclonal antibody treatment of severe autoimmune hemolytic anemia due to warm reactive IgM autoantibody in a child with common variable immunodeficiency. Am J Hematol. 2004;76(2):152-5.
37. Hongeng S, Tardtong P, Worapongpaiboon S, Ungkanont A, Jootar S. Successful treatment of refractory autoimmune haemolytic anaemia in a post-unrelated bone marrow transplant paediatric patient with rituximab. Bone Marrow Transplant. 2002;29(10):871-2.
38. Makis A, Kanta Z, Kalogeropoulos D, Chaliasos N. Anti-CD20 Treatment of Autoimmune Hemolytic Anemia Refractory to Corticosteroids and Azathioprine: A Pediatric Case Report and Mini Review. Case Rep Hematol. 2018;2018:8471073.
39. Mueller BU, Bennett CM, Feldman HA, Bussel JB, Abshire TC, Moore TB, et al. One year follow-up of children and adolescents with chronic immune thrombocytopenic purpura (ITP) treated with rituximab. Pediatr Blood Cancer. 2009;52(2):259-62.
40. Kim JJ, Thrasher AJ, Jones AM, Davies EG, Cale CM. Rituximab for the treatment of autoimmune cytopenias in children with immune deficiency. British J Haematol. 2007;138(1):94-6.
41. Parodi E, Rivetti E, Amendola G, Bisogno G, Calabrese R, Farruggia P, et al. Long-term follow-up analysis after rituximab therapy in children with refractory symptomatic ITP: identification of factors predictive of a sustained response. Br J Haematol. 2009;144(4):552-8.
42. Taube T, Schmid H, Reinhard H, von Stackelberg A, Overberg US. Effect of a single dose of rituximab in chronic immune thrombocytopenic purpura in childhood. Haematologica. 2005;90(2):281-3.
43. Patel VL, Mahévas M, Lee SY, Stasi R, Cunningham-Rundles S, Godeau B, et al. Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood. 2012;119(25):5989-95.
44. Labrosse R, Barmettler S, Derfalvi B, Blincoe A, Cros G, Lacombe-Barrios J, et al. Rituximab-induced hypogammaglobulinemia and infection risk in pediatric patients. J Allergy Clin Immunol. 2021;148(2):523-32.e8.
45. Ottaviano G, Marinoni M, Graziani S, Sibson K, Barzaghi F, Bertolini P, et al. Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia. J Allergy Clin Immunol Pract. 2020;8(1):273-82.
46. Ducassou S, Leverger G, Fernandes H, Chambost H, Bertrand Y, Armari-Alla C, et al. Benefits of rituximab as a second-line treatment for autoimmune haemolytic anaemia in children: a prospective French cohort study. British J Haematol. 2017;177(5):751-8.
2. Notarangelo LD, Bacchetta R, Casanova JL, Su HC. Human inborn errors of immunity: An expanding universe. Sci Immunol. 2020;5(49).
3. Fischer A, Provot J, Jais JP, Alcais A, Mahlaoui N. Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies. J Allergy Clin Immunology. 2017;140(5):1388-93.e8.
4. Leiding JW, Forbes LR. Mechanism-Based Precision Therapy for the Treatment of Primary Immunodeficiency and Primary Immunodysregulatory Diseases. J Allergy Clin Immunol Practice. 2019;7(3):761-73.
5. Barmettler S, Ong MS, Farmer JR, Choi H, Walter
J. Association of Immunoglobulin Levels, Infectious
Risk, and Mortality With Rituximab and Hypogammaglobulinemia. JAMA. 2018;1(7):e184169.
6. Kaplan B, Kopyltsova Y, Khokhar A, Lam F, Bonagura V. Rituximab and immune deficiency: case series and review of the literature. J Allergy Clin Immunol Practice. 2014;2(5):594-600.
7. Pecoraro A, Crescenzi L, Galdiero MR, Marone G, Rivellese F, Rossi FW, et al. Immunosuppressive therapy with rituximab in common variable immunodeficiency. Clin Mol Allergy. 2019;17:9.
8. Azizi G, Ziaee V, Tavakol M, Alinia T, Yazdai R, Mohammadi H, et al. Approach to the Management of Autoimmunity in Primary Immunodeficiency. Scand J Immunol. 2017;85(1):13-29.
9. Food, Administration D. Highlights of Prescribing Information (Rituxan).
10. Kasi PM, Tawbi HA, Oddis CV, Kulkarni HS. Clinical review: Serious adverse events associated with the use of rituximab - a critical care perspective. Critical care. 2012;16(4):231.
11. Zian Z, Berry SPD, Bahmaie N, Ghotbi D, Kashif A, Madkaikar M, et al. The clinical efficacy of Rituximab administration in autoimmunity disorders, primary immunodeficiency diseases and malignancies. Int Immunopharmacol. 2021;95:107565.
12. Seidel MG, Kindle G, Gathmann B, Quinti I, Buckland M, van Montfrans J, et al. The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity. The journal of allergy and clinical immunology In practice. 2019;7(6):1763-70.
13. Amaya-Uribe L, Rojas M, Azizi G, Anaya JM, Gershwin ME. Primary immunodeficiency and autoimmunity: A comprehensive review. J Autoimmunity. 2019;99:52-72.
14. Bardou MLD, Henriques MT, Grumach AS. Inborn errors of immunity associated with characteristic phenotypes. Jornal de pediatria. 2021;97 Suppl 1(Suppl 1):S75-s83.
15. Bousfiha A, Jeddane L, Picard C, Al-Herz W, Ailal F, Chatila T, et al. Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification. J Clin Immunol. 2020;40(1):66-81.
16. Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood advances. 2019;3(23):3829-66.
17. Program CTE. Common terminology criteria for adverse events (CTCAE). v. 5.0 [5x7]. Cancer ther Eval Progr. 2017.
18. Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386-93.
19. McLaughlin P, Grillo-López AJ, Link BK, Levy R, Czuczman MS, Williams ME, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Cin Oncol. 1998;16(8):2825-33.
20. England N. Clinical commissioning policy statement: biologic therapies for the treatment of juvenile idiopathic arthritis (JIA). 2015. Contract No: NHS England E03X04 E.3.
21. Herrero-Morant A, Álvarez-Reguera C, Martín-Varillas JL, Calvo-Río V, Casado A, Prieto-Peña D, et al. Biologic Therapy in Refractory Non-Multiple Sclerosis Optic Neuritis Isolated or Associated to Immune-Mediated Inflammatory Diseases. A Multicenter Study. J Clin Med. 2020;9(8).
22. Marciano BE, Holland SM. Primary Immunodeficiency Diseases: Current and Emerging Therapeutics. Front Immunol. 2017;8:937.
23. Zecca M, De Stefano P, Nobili B, Locatelli F. Anti-CD20 monoclonal antibody for the treatment of severe, immune-mediated, pure red cell aplasia and hemolytic anemia. Blood. 2001;97(12):3995-7.
24. Rao A, Kelly M, Musselman M, Ramadas J, Wilson D, Grossman W, et al. Safety, efficacy, and immune reconstitution after rituximab therapy in pediatric patients with chronic or refractory hematologic autoimmune cytopenias. Pediatric Blood Cancer. 2008;50(4):822-5.
25. Wang J, Wiley JM, Luddy R, Greenberg J, Feuerstein MA, Bussel JB. Chronic immune thrombocytopenic purpura in children: assessment of rituximab treatment. J Pediatrics. 2005;146(2):217-21.
26. Serris A, Amoura Z, Canouï-Poitrine F, Terrier B, Hachulla E, Costedoat-Chalumeau N, et al. Efficacy and safety of rituximab for systemic lupus erythematosus-associated immune cytopenias: A multicenter retrospective cohort study of 71 adults. Ame J Hematol. 2018;93(3):424-9.
27. Zecca M, Nobili B, Ramenghi U, Perrotta S, Amendola G, Rosito P, et al. Rituximab for the treatment of refractory autoimmune hemolytic anemia in children. Blood. 2003;101(10):3857-61.
28. Ajmi H, Mabrouk S, Hassayoun S, Regaieg H, Tfifha M, Jalel C, et al. Success of anti-CD20 monoclonal antibody treatment for severe autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, and immunoglobulin M autoantibodies in a child: a case report. J Med Case Rep. 2017;11(1):321.
29. Ansari S, Tashvighi M, Darbandi B, Salimi AB, Golpaygani M. Rituximab for child with chronic relapsing autoimmune hemolytic anemia. Pediatric Hematol Oncol. 2011;28(2):164-6.
30. Dev M, Mushtaq N, Faisal A. A case of autoimmune haemolytic anaemia achieving complete response with rituximab. J Pak Med Assoc. 2014;64(6):700-2.
31. Gottardo NG, Baker DL, Willis FR. Successful induction and maintenance of long-term remission in a child with chronic relapsing autoimmune hemolytic anemia using rituximab. Pediatr Hematol Oncol. 2003;20(7):557-61.
32. Kuzmanovic M, Jurisic V. Rituximab for treatment of autoimmune hemolytic anemia. Indian pediatr. 2012;49(8):672-4.
33. Makadia D, Siddaiahgari SR, Latha MS. Anti B cell targeted therapy for autoimmune hemolytic anemia in an infant. Indian J Pharmacol. 2013;45(5):526-7.
34. Moriya K, Matsuhashi T, Onuma M, Niizuma H, Rikiishi T, Asada H, et al. Successful treatment with rituximab of an infant with refractory autoimmune hemolytic anemia. Int J Hematol. 2013;98(2):237-9.
35. Quartier P, Brethon B, Philippet P, Landman-Parker J, Le Deist F, Fischer A. Treatment of childhood autoimmune haemolytic anaemia with rituximab. Lancet. 2001;358(9292):1511-3.
36. Wakim M, Shah A, Arndt PA, Garratty G, Weinberg K, Hofstra T, et al. Successful anti-CD20 monoclonal antibody treatment of severe autoimmune hemolytic anemia due to warm reactive IgM autoantibody in a child with common variable immunodeficiency. Am J Hematol. 2004;76(2):152-5.
37. Hongeng S, Tardtong P, Worapongpaiboon S, Ungkanont A, Jootar S. Successful treatment of refractory autoimmune haemolytic anaemia in a post-unrelated bone marrow transplant paediatric patient with rituximab. Bone Marrow Transplant. 2002;29(10):871-2.
38. Makis A, Kanta Z, Kalogeropoulos D, Chaliasos N. Anti-CD20 Treatment of Autoimmune Hemolytic Anemia Refractory to Corticosteroids and Azathioprine: A Pediatric Case Report and Mini Review. Case Rep Hematol. 2018;2018:8471073.
39. Mueller BU, Bennett CM, Feldman HA, Bussel JB, Abshire TC, Moore TB, et al. One year follow-up of children and adolescents with chronic immune thrombocytopenic purpura (ITP) treated with rituximab. Pediatr Blood Cancer. 2009;52(2):259-62.
40. Kim JJ, Thrasher AJ, Jones AM, Davies EG, Cale CM. Rituximab for the treatment of autoimmune cytopenias in children with immune deficiency. British J Haematol. 2007;138(1):94-6.
41. Parodi E, Rivetti E, Amendola G, Bisogno G, Calabrese R, Farruggia P, et al. Long-term follow-up analysis after rituximab therapy in children with refractory symptomatic ITP: identification of factors predictive of a sustained response. Br J Haematol. 2009;144(4):552-8.
42. Taube T, Schmid H, Reinhard H, von Stackelberg A, Overberg US. Effect of a single dose of rituximab in chronic immune thrombocytopenic purpura in childhood. Haematologica. 2005;90(2):281-3.
43. Patel VL, Mahévas M, Lee SY, Stasi R, Cunningham-Rundles S, Godeau B, et al. Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood. 2012;119(25):5989-95.
44. Labrosse R, Barmettler S, Derfalvi B, Blincoe A, Cros G, Lacombe-Barrios J, et al. Rituximab-induced hypogammaglobulinemia and infection risk in pediatric patients. J Allergy Clin Immunol. 2021;148(2):523-32.e8.
45. Ottaviano G, Marinoni M, Graziani S, Sibson K, Barzaghi F, Bertolini P, et al. Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia. J Allergy Clin Immunol Pract. 2020;8(1):273-82.
46. Ducassou S, Leverger G, Fernandes H, Chambost H, Bertrand Y, Armari-Alla C, et al. Benefits of rituximab as a second-line treatment for autoimmune haemolytic anaemia in children: a prospective French cohort study. British J Haematol. 2017;177(5):751-8.
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| Autoimmune diseases Primary Immunodeficiency diseases Rituximab | ||
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How to Cite
1.
Sharafian S, Mohammadi M, Alavi S, Mesdaghi M, Shiari R, Shamsian BS, Eshghi P, Haji Khodaverdi Khani H, Abolghasemi H, Karimi A, Behniafard N, Mollaei Tavana P, Nasehi MM, Hashemieh M, Khodashenas M, Jamee M, Chavoshzadeh Z, Eslami N. A Report on the Clinical Efficacy of Rituximab Administration in Patients with Inborn Errors of Immunity and Autoimmune/Autoinflammatory Manifestations. Iran J Allergy Asthma Immunol. 2025;:1-14.
