Joint inflammation in patients with primary immunodeficiency


  • O.A. Oshlіanska Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine
  • T.G. Nadtochiу SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine», Kyiv, Ukraine
  • A.P. Volokha Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine
  • S.I. Tolkach SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine», Kyiv, Ukraine



children, primary immunodeficiencies, arthritis, Nijmegen syndrome


Purpose - to analyse the leading markers of primary immunodeficiencies in children with joint syndrome based on a clinical case study.

The article presents literature data on one of the immunopathological syndromes - autoimmune syndrome - in children with primary immunodeficiencies. Mechanisms of autoimmunity and frequency of joint lesions are discussed. It is emphasized that mostly lesions of the musculoskeletal system are observed in patients with primary disorders of antibody formation and in certain primary combined immunodeficiencies. It was noted that there are specific features of damage to the musculoskeletal system in various nosological units of primary immunodeficiencies. Basic ideas about modern opportunities and problems of treatment of joint lesions in children with primary immunodeficiencies are given. The main clinical manifestations of Nijmegen syndrome in children are described. A case of joint damage in a child with Nijmegen syndrome is given.

Conclusions. The system of treatment of autoimmune pathology in the setting of primary genetically determined disorders of the immune system requires further improvement, given the increasing survival rate of patients with primary immunodeficiencies, and in recent years there is a need to develop consensus recommendations for their management, which will improve their quality of life.

The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies.

No conflict of interests was declared by the authors.

Author Biography

O.A. Oshlіanska, Shupyk National Healthcare University of Ukraine, Kyiv

SI “Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine”, Kyiv


Abbott JK, Gelfand EW. (2022, Jun). Registries are shaping how we think about primary immunodeficiency diseases. Journal of Allergy and Clinical Immunology. 149; 6: 1943-1945.; PMid:35487306

Amaya-Uribe L, Rojas M, Azizi G, Anaya JM, Gershwin ME. (2019, May). Primary immunodeficiency and autoimmunity: A comprehensive review. J Autoimmun. 99: 52-72. Epub 2019 Feb 20.; PMid:30795880

Anaya J-M. (2014, Apr-May). The diagnosis and clinical significance of polyautoimmunity. Autoimmunity Reviews. 13; 4-5: 423-426.; PMid:24424171

Antypkin YuH, Okhotnikova OM, Oshlianska OA, Omelchenko LI. (2019). Problemni pytannia dytiachoi revmatolohii. Monohrafiia. Za redaktsiieiu Antypkina Yu.H., Okhotnikovoi O.M., Oshlianskoi O.A., Omelchenko L.I. Kyiv: «Lohos»: 700.

Azizi G, Kiaee F, Hedayat E. (2018). Rheumatologic complications in a cohort of 227 patients with common variable immunodeficiency. Scand J Immunol. 87: e12663.; PMid:29574865

Azizi G, Pouyani MR, Abolhassani H. (2016, Dec). Cellular and molecular mechanisms of immune dysregulation and autoimmunity. Cellular Immunology. 310: 14-26.; PMid:27614846

Azizi G, Yazdani R, Rae W. (2018, Oct). Monogenic polyautoimmunity in primary immunodeficiency diseases. 17; 10: 1028-1039.; PMid:30107266

Barzaghi F, Passerini L. (2021, Feb 22). IPEX Syndrome: Improved Knowledge of Immune Pathogenesis Empowers Diagnosis. Front. Pediatr., Sec. Pediatric Immunology. 9: 612760.;PMid:33692972 PMCid:PMC7937806

Blazina Š, Markelj G, Jeverica KA. (2016). Autoimmune and Inflammatory Manifestations in 247 Patients with Primary Immunodeficiency - a Report from the Slovenian National Registry. Journal of Clinical Immunology. 36: 764-773.; PMid:27582173

Bondarenko AV, Volokha AP, Chernyshova LI, Kostyuchenko LV. (2018). Autoimmune diseases in children with primary antibody deficiencies. Sovremennaya pediatriya. 2(90): 9-13.

Boyarchuk O, Volyanska LA, Kovalchuk T, Kinash M. (2017, Mar). Arthritis in primary immunodeficiencies. Pain joints spine. 7; 1: 1-6.

CEREDIH: The French PID study group. (2010, May). The French national registry of primary immunodeficiency diseases. Clinical Immunology. 135; 2: 264-272.; PMid:20399414

Cunningham-Rundles C, Bodian C. (1999). Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 92: 34-48.; PMid:10413651

Demirdag YY, Gupta S. (2023). Infections in DNA Repair Defects. Pathogens. 12: 440.; PMid:36986362 PMCid:PMC10054915

Farmer JR, Foldvari Z, Ujhazi B. (2019, Jul-Aug). Outcomes and Treatment Strategies for Autoimmunity and Hyperinflammation in Patients with RAG Deficiency. The Journal of Allergy and Clinical Immunology: In Practice. 7; 6: 1970-1985.e4.

Filipiuk A, Kozakiewicz A, Kośmider K. (2022). Diagnostic and therapeutic approach to children with Nijmegen breakage syndrome in relation to development of lymphoid malignancies. Annals of Agricultural and Environmental Medicine. 29; 2: 207-214.; PMid:35767752

Fischer A, Provot J, Jais JP, Alcais A, Mahlaoui N et al. (2017, Nov). Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies. J Allergy Clin Immunol. 140(5): 1388-1393.e8. Epub 2017 Feb 10.; PMid:28192146

Goyal R, Bulua AC, Nikolov NP. (2009, Jan). Rheumatologic and Autoimmune Manifestations of Primary Immunodeficiency Disorders. Curr Opin Rheumatol. 21(1): 78-84.; PMid:19077721 PMCid:PMC2760066

Hans-Hartmut P. (2013). Adult-onset immunodefi ciency - why is it important in rheumatology? Arthritis Research & Therapy. 15: 105. URL:; PMid:23363560 PMCid:PMC3745649

Hasbaoui BE, Elyajouri A, Abilkassem R et al. (2020). Nijmegen breakage syndrome: case report and review of literature. Pan African Medical Journal. 35: 85.

Hiel JA, Weemaes CM, van den Heuvel LP. (2000). Nijmegen breakage syndrome. The International Nijmegen Breakage Syndrome Study Group. Arch Dis Child. 82: 400-406.; PMid:10799436 PMCid:PMC1718318

Kaplan MYi, Ozen S, Akcal O et al. (2020). GenelAutoimmune and inflammatory manifestations in pediatric patients with primary immunodeficiencies and their importance as a warning sign. Allergol Immunopathol (Madr). 48(6): 701-710.; PMid:32446782

Khoury T, Molho-Pessach V, Ramot Y, Ayman AR, Elpeleg O, Berkman N et al. (2017, Feb). Tocilizumab Promotes Regulatory T-cell Alleviation in STAT3 Gain-of-function-associated Multi-organ Autoimmune Syndrome. Clin Ther. 39(2): 444-449. Epub 2017 Jan 30.; PMid:28153428

Kitcharoensakkula M, Cooper MA. (2019). Rheumatologic and autoimmune manifestations in primary immune deficiency. Curr Opin Allergy Clin Immunol. 19: 545-552.; PMid:31425194

Massaad MJ, Zainal M, Al-Herz W et al. (2020). Frequency and Manifestations of Autoimmunity Among Children Registered in the Kuwait National Primary Immunodeficiency Registry. Front. Immunol. 11: 1119.; PMid:32582199 PMCid:PMC7280554

Mellouli F, Mustapha IB, Khaled MB. (2015). Report of the Tunisian Registry of Primary Immunodeficiencies: 25-Years of Experience (1988-2012). Journal of Clinical Immunology. 35: 745-753.; PMid:26464197

Mohammadi F, Yadegar A, Mardani M, Ayati A, Abolhassani H, Rezaei N. (2023, Apr). Organ-based clues for diagnosis of inborn errors of immunity: A practical guide for clinicians. Immun Inflamm Dis. 11(4): e833.; PMid:37102642 PMCid:PMC10091206

Mormile I, Punziano A, Riolo CA et al. (2021). Common Variable Immunodeficiency and Autoimmune Diseases: A Retrospective Study of 95 Adult Patients in a Single Tertiary Care Center. Front Immunol. 12: 652487. Published online 2021 Jul 5.; PMid:34290696 PMCid:PMC8287325

Oshlianska OA, Krat VV, Zakharchuk OV, Hladun IV. (2016). Revmatoidopodibni urazhennia u khvorykh z defitsytom antytiloutvorennia (klinichnyi vypadok). Klinichna alerholohiia Alerholohiia. Infektolohiia. 2 (91): 21-24.

Oshlianska OA, Nikolayenko VB. (2016). Aseptic arthritis in children associated with primary immune deficiencies. PReS. Genova: 60.

Oshlianska OA, Petrenko LB. (2013). Masky revmatychnykh khvorob u ditei yak proiavy pervynnykh imunodefitsytiv (klinichni vypadky) Klinichna imunolohiia i alerholohiia. 4 (63): 51-56.

Pieniawska-Śmiech K, Lewandowicz-Uszyńska A, Zemelka-Wiacek M et al. (2023). Assessment of autoantibodies in paediatric population with primary immunodeficiencies: a pilot study. BMC Immunology. 24: 8.; PMid:37270495 PMCid:PMC10238767

Pott NM, Atschekzei F, Pott CC, Ernst D, Witte T, Sogkas G. (2022, Dec). Primary antibody deficiency-associated arthritis shares features with spondyloarthritis and enteropathic arthritis. RMD Open. 8(2): e002664.; PMid:36583733 PMCid:PMC9730402

Saifi M, Wysocki CA. (2015, Nov). Autoimmune Disease in Primary Immunodeficiency: At the Crossroads of Anti-Infective Immunity and Self-Tolerance. Immunol Allergy Clin North Am. 35(4): 731-752. Epub 2015 Sep 4.; PMid:26454316

Seidel MG. (2014). Autoimmune and other cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment. Blood. 124: 2337-2344.; PMid:25163701 PMCid:PMC4192747

Škvorc HM, Anzić SA, Jerković I et al. (2023). Allergic Rhinitis and Other Allergic and Autoimmune Disorders in Children with IgA Deficiency. J App Med Sci. ISSN 2347-954X (Print); ISSN 2320-6691 (Online). Journal homepage:

Swierkot J, Lewandowicz-Uszynska A, Chlebicki A et al. (2006). Rheumatoid Arthritis in a Patient with Common Variable Immunodeficiency: Difficulty in Diagnosis and Therapy. Clin Rheumatol. 25: 92-94.; PMid:15940551

Szabó MZ. (2018, Jun). Rheumatological manifestations in primary immunodeficiency diseases. Orvosi Hetilap. 159 (23): 919-928.; PMid:29860881

Varon R, Demuth I, Chrzanowska KH. (1999, May 17). Nijmegen Breakage Syndrome. [Updated 2022 Aug 18]. In: Adam MP, Mirzaa GM, Pagon RA et al. editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Bookshelf URL:

Venkatachari IV, Chougule A, Gowri V, Taur P, Bodhanwala M, Prabhu S, Madkaikar M, Desai M. (2023). Monogenic inborn errors of immunity in autoimmune disorders. Immunol Res. 71(5): 771-780. Epub 2023 May 18.; PMid:37199901

Walter JE, Farmer JR, Foldvari Z et al. (2016). Mechanism-based strategies for the management of autoimmunity and immune dysregulation in primary immunodeficiencies. Allergy Clin Immunol Pract. 4(6): 1089-1100.; PMid:27836058 PMCid:PMC5289744

Wang W, Liu L, Hui X, Wang Y, Ying W, Zhou Q et al. (2021, Mar 17). Efficacy of tocilizumab therapy in a patient with severe pancytopenia associated with a STAT3 gain-of-function mutation. BMC Immunol. 22(1): 19.; PMid:33731004 PMCid:PMC7968248

Wu KY, Purswani P, Ujhazi B. (2019). Arthritis in Two Patients with Partial Recombination Activating Gene Deficiency. Front. Pediatr. 7: 235.; PMid:31334206 PMCid:PMC6625222