Joint Involvement in Patients with LPS-Responsive and Beige-Like Anchor Protein (LRBA) Deficiency: A Case Report and Literature Review
-
Seyed Erfan Rasouli
,
Niusha Sharifinejad
,
Mahnaz Jamee
,
Mazdak Fallahi
,
Seyedeh Atefeh Hashemi Moghaddam
,
Mahsa Rekabi
,
Zahra Daneshmandi
,
Seyed Alireza Mahdaviani
,
Ali Akbar Velayati
Abstract
Background: Lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency is an inborn error of immunity characterized by a heterogeneous spectrum of manifestations, including enteropathy, immune dysregulation, and autoimmune disorder. Joint involvement has been less frequently reported, and limited data regarding its clinical presentation in LRBA deficiency has been published.
Case presentation and review results: We reported an Iranian girl who was initially presented with recurrent respiratory tract infections and otitis media, later complicated by arthritis, growth failure, and organomegaly. The diagnosis of LRBA deficiency was confirmed by the identification of a novel homozygous missense variant in the LRBA gene (c.7742T>A, p.M2581K). Along with this report, a literature review focused on joint involvement, on 26 patients with LRBA deficiency was performed.
Conclusion: Non-infectious manifestations such as joint involvement have a broad spectrum in LRBA deficiency. For the timely diagnosis and appropriate clinical management, LRBA deficiency should always be kept in mind as a differential diagnosis in patients with joint involvement and clinically typical immune dysregulation.
1. Gámez-Díaz L, August D, Stepensky P, Revel-Vilk S, Seidel MG, Noriko M, et al. The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency. J Allergy Clin Immunol. 2016;137(1):223-230.
2. Lopez-Herrera G, Tampella G, Pan-Hammarström Q, Herholz P, Trujillo-Vargas CM, Phadwal K, et al. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am J Hum Genet. 2012;90(6):986-1001.
3. Bal SK, Haskologlu S, Serwas NK, Islamoglu C, Aytekin C, Kendirli T, et al. Multiple presentations of LRBA deficiency: a single-center experience. J Clin Immunol. 2017;37(8):790-800.
4. Ghaini M, Arzanian MT, Shamsian BS, Sadr S, Rohani P, Keramatipour M, et al. Identifying Novel Mutations in Iranian Patients with LPS-responsive Beige-like Anchor Protein (LRBA) Deficiency. Immunol Invest. 2021;50(4):399-405.
5. Oz RS, Tesher MS. Arthritis in children with LRBA deficiency–case report and literature review. Pediatr Rheumatol Online J. 2019;17(1):82.
6. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-24.
7. Bratanič N, Kovač J, Pohar K, Podkrajšek KT, Ihan A, Battelino T, et al. Multifocal gastric adenocarcinoma in a patient with LRBA deficiency. Orphanet J Rare Dis. 2017;12(1):131.
8. Kiykim A, Ogulur I, Dursun E, Charbonnier LM, Nain E, Cekic S, et al. Abatacept as a long-term targeted therapy for LRBA deficiency. J Allergy Clin Immunol Pract. 2019;7(8):2790-2800.e15.
9. Alkhairy OK, Abolhassani H, Rezaei N, Fang M, Andersen KK, Chavoshzadeh Z, et al. Spectrum of phenotypes associated with mutations in LRBA. J Clin Immunol. 2016;36(1):33-45.
10. Sun D, Heimall J. Disorders of CTLA-4 expression, how they lead to CVID and dysregulated immune responses. Curr Opin Allergy Clin Immunol. 2019;19(6):578-585.
11. Charbonnier L-M, Janssen E, Chou J, Ohsumi TK, Keles S, Hsu JT, et al. Regulatory T-cell deficiency and immune dysregulation, polyendocrinopathy, enteropathy, X-linked–like disorder caused by loss-of-function mutations in LRBA. J Allergy Clin Immunol. 2015;135(1):217-27.
12. Serwas NK, Kansu A, Santos-Valente E, Kuloğlu Z, Demir A, Yaman A, et al. Atypical manifestation of LRBA deficiency with predominant IBD-like phenotype. Inflamm Bowel Dis. 2015;21(1):40-7.
13. Meshaal S, El Hawary R, Adel R, Abd Elaziz D, Erfan A, Lotfy S, et al. Clinical Phenotypes and Immunological Characteristics of 18 Egyptian LRBA Deficiency Patients. J Clin Immunol. 2020;40(6):820-832.
14. De Bruyne M, Bogaert DJ, Venken K, Van den Bossche L, Bonroy C, Roels L, et al. A novel LPS-responsive beige-like anchor protein (LRBA) mutation presents with normal cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and overactive TH17 immunity. J Allergy Clin Immunol. 2018;142(6):1968-1971.
15. Azizi G, Abolhassani H, Mahdaviani SA, Chavoshzadeh Z, Eshghi P, Yazdani R, et al. Clinical, immunologic, molecular analyses and outcomes of iranian patients with LRBA deficiency: a longitudinal study. Pediatr Allergy Immunol. 2017;28(5):478-484.
16. Mozdarani H, Kiaee F, Fekrvand S, Azizi G, Yazdani R, Zaki-Dizaji M, et al. G2-lymphocyte chromosomal radiosensitivity in patients with LPS responsive beige-like anchor protein (LRBA) deficiency. Int J Radiat Biol. 2019;95(6):680-690.
17. Sari S, Dogu F, Hwa V, Haskologlu S, Dauber A, Rosenfeld R, et al. A successful HSCT in a girl with novel LRBA mutation with refractory celiac disease. J Clin Immunol. 2016;36(1):8-11.
18. Alangari A, Alsultan A, Adly N, Massaad MJ, Kiani IS, Aljebreen A, et al. LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency. J Allergy Clin Immunol. 2012;130(2):481-8.e2.
19. Al-Mayouf SM, Naji H, Alismail K, Alazami AM, Sheikh F, Conca W, et al. Evolving spectrum of LRBA deficiency-associated chronic arthritis: is there a causative role in juvenile idiopathic arthritis? Clin Exp Rheumatol. 2017;35(2):327-329.
20. Shamriz O, Shadur B, NaserEddin A, Zaidman I, Simanovsky N, Elpeleg O, et al. Respiratory manifestations in LPS-responsive beige-like anchor (LRBA) protein-deficient patients. Eur J Pediatr. 2018;177(8):1163-1172.
21. Al Sukaiti N, AbdelRahman K, AlShekaili J, Al Oraimi S, Al Sinani A, Al Rahbi N, et al. Agammaglobulinaemia despite terminal B‐cell differentiation in a patient with a novel LRBA mutation. Clin Transl Immunology. 2017;6(5):e144.
22. Azizi G, Abolhassani H, Yazdani R, Mohammadikhajehdehi S, Parvaneh N, Negahdari B, et al. New therapeutic approach by sirolimus for enteropathy treatment in patients with LRBA deficiency. Eur Ann Allergy Clin Immunol. 2017;49(5):235-239.
23. Cagdas D, Halaçlı SO, Tan Ç, Lo B, Çetinkaya PG, Esenboğa S, et al. A spectrum of clinical findings from ALPS to CVID: several novel LRBA defects. J Clin Immunol. 2019;39(7):726-738.
24. Yang L, Xue X, Chen X, Wu J, Yang X, Xu L, et al. Abatacept is effective in Chinese patients with LRBA and CTLA4 deficiency. Genes & Diseases. 2020.
25. Seidel MG, Böhm K, Dogu F, Worth A, Thrasher A, Florkin B, et al. Treatment of severe forms of LPS-responsive beige-like anchor protein deficiency with allogeneic hematopoietic stem cell transplantation. J Allergy Clin Immunol. 2018;141(2):770-775.e1.
26. Lévy E, Stolzenberg M-C, Bruneau J, Breton S, Neven B, Sauvion S, et al. LRBA deficiency with autoimmunity and early onset chronic erosive polyarthritis. Clin Immunol. 2016;168:88-93.
27. Lo B, Zhang K, Lu W, Zheng L, Zhang Q, Kanellopoulou C, et al. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science. 2015;349(6246):436-40.
28. Sharapova SO, Haapaniemi E, Sakovich IS, Rojas J, Gámez-Díaz L, Mareika YE, et al. Novel LRBA mutation and possible germinal mosaicism in a Slavic family. J Clin Immunol. 2018;38(4):471-474.
29. Liphaus BL, Caramalho I, Rangel-Santos A, Silva CA, Demengeot J, Carneiro-Sampaio MMS. LRBA deficiency: a new genetic cause of monogenic lupus. Ann Rheum Dis. 2020;79(3):427-428.
30. Tesch VK, Abolhassani H, Shadur B, Zobel J, Mareika Y, Sharapova S, et al. Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score. J Allergy Clin Immunol. 2020;145(5):1452-1463.
2. Lopez-Herrera G, Tampella G, Pan-Hammarström Q, Herholz P, Trujillo-Vargas CM, Phadwal K, et al. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am J Hum Genet. 2012;90(6):986-1001.
3. Bal SK, Haskologlu S, Serwas NK, Islamoglu C, Aytekin C, Kendirli T, et al. Multiple presentations of LRBA deficiency: a single-center experience. J Clin Immunol. 2017;37(8):790-800.
4. Ghaini M, Arzanian MT, Shamsian BS, Sadr S, Rohani P, Keramatipour M, et al. Identifying Novel Mutations in Iranian Patients with LPS-responsive Beige-like Anchor Protein (LRBA) Deficiency. Immunol Invest. 2021;50(4):399-405.
5. Oz RS, Tesher MS. Arthritis in children with LRBA deficiency–case report and literature review. Pediatr Rheumatol Online J. 2019;17(1):82.
6. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-24.
7. Bratanič N, Kovač J, Pohar K, Podkrajšek KT, Ihan A, Battelino T, et al. Multifocal gastric adenocarcinoma in a patient with LRBA deficiency. Orphanet J Rare Dis. 2017;12(1):131.
8. Kiykim A, Ogulur I, Dursun E, Charbonnier LM, Nain E, Cekic S, et al. Abatacept as a long-term targeted therapy for LRBA deficiency. J Allergy Clin Immunol Pract. 2019;7(8):2790-2800.e15.
9. Alkhairy OK, Abolhassani H, Rezaei N, Fang M, Andersen KK, Chavoshzadeh Z, et al. Spectrum of phenotypes associated with mutations in LRBA. J Clin Immunol. 2016;36(1):33-45.
10. Sun D, Heimall J. Disorders of CTLA-4 expression, how they lead to CVID and dysregulated immune responses. Curr Opin Allergy Clin Immunol. 2019;19(6):578-585.
11. Charbonnier L-M, Janssen E, Chou J, Ohsumi TK, Keles S, Hsu JT, et al. Regulatory T-cell deficiency and immune dysregulation, polyendocrinopathy, enteropathy, X-linked–like disorder caused by loss-of-function mutations in LRBA. J Allergy Clin Immunol. 2015;135(1):217-27.
12. Serwas NK, Kansu A, Santos-Valente E, Kuloğlu Z, Demir A, Yaman A, et al. Atypical manifestation of LRBA deficiency with predominant IBD-like phenotype. Inflamm Bowel Dis. 2015;21(1):40-7.
13. Meshaal S, El Hawary R, Adel R, Abd Elaziz D, Erfan A, Lotfy S, et al. Clinical Phenotypes and Immunological Characteristics of 18 Egyptian LRBA Deficiency Patients. J Clin Immunol. 2020;40(6):820-832.
14. De Bruyne M, Bogaert DJ, Venken K, Van den Bossche L, Bonroy C, Roels L, et al. A novel LPS-responsive beige-like anchor protein (LRBA) mutation presents with normal cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and overactive TH17 immunity. J Allergy Clin Immunol. 2018;142(6):1968-1971.
15. Azizi G, Abolhassani H, Mahdaviani SA, Chavoshzadeh Z, Eshghi P, Yazdani R, et al. Clinical, immunologic, molecular analyses and outcomes of iranian patients with LRBA deficiency: a longitudinal study. Pediatr Allergy Immunol. 2017;28(5):478-484.
16. Mozdarani H, Kiaee F, Fekrvand S, Azizi G, Yazdani R, Zaki-Dizaji M, et al. G2-lymphocyte chromosomal radiosensitivity in patients with LPS responsive beige-like anchor protein (LRBA) deficiency. Int J Radiat Biol. 2019;95(6):680-690.
17. Sari S, Dogu F, Hwa V, Haskologlu S, Dauber A, Rosenfeld R, et al. A successful HSCT in a girl with novel LRBA mutation with refractory celiac disease. J Clin Immunol. 2016;36(1):8-11.
18. Alangari A, Alsultan A, Adly N, Massaad MJ, Kiani IS, Aljebreen A, et al. LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency. J Allergy Clin Immunol. 2012;130(2):481-8.e2.
19. Al-Mayouf SM, Naji H, Alismail K, Alazami AM, Sheikh F, Conca W, et al. Evolving spectrum of LRBA deficiency-associated chronic arthritis: is there a causative role in juvenile idiopathic arthritis? Clin Exp Rheumatol. 2017;35(2):327-329.
20. Shamriz O, Shadur B, NaserEddin A, Zaidman I, Simanovsky N, Elpeleg O, et al. Respiratory manifestations in LPS-responsive beige-like anchor (LRBA) protein-deficient patients. Eur J Pediatr. 2018;177(8):1163-1172.
21. Al Sukaiti N, AbdelRahman K, AlShekaili J, Al Oraimi S, Al Sinani A, Al Rahbi N, et al. Agammaglobulinaemia despite terminal B‐cell differentiation in a patient with a novel LRBA mutation. Clin Transl Immunology. 2017;6(5):e144.
22. Azizi G, Abolhassani H, Yazdani R, Mohammadikhajehdehi S, Parvaneh N, Negahdari B, et al. New therapeutic approach by sirolimus for enteropathy treatment in patients with LRBA deficiency. Eur Ann Allergy Clin Immunol. 2017;49(5):235-239.
23. Cagdas D, Halaçlı SO, Tan Ç, Lo B, Çetinkaya PG, Esenboğa S, et al. A spectrum of clinical findings from ALPS to CVID: several novel LRBA defects. J Clin Immunol. 2019;39(7):726-738.
24. Yang L, Xue X, Chen X, Wu J, Yang X, Xu L, et al. Abatacept is effective in Chinese patients with LRBA and CTLA4 deficiency. Genes & Diseases. 2020.
25. Seidel MG, Böhm K, Dogu F, Worth A, Thrasher A, Florkin B, et al. Treatment of severe forms of LPS-responsive beige-like anchor protein deficiency with allogeneic hematopoietic stem cell transplantation. J Allergy Clin Immunol. 2018;141(2):770-775.e1.
26. Lévy E, Stolzenberg M-C, Bruneau J, Breton S, Neven B, Sauvion S, et al. LRBA deficiency with autoimmunity and early onset chronic erosive polyarthritis. Clin Immunol. 2016;168:88-93.
27. Lo B, Zhang K, Lu W, Zheng L, Zhang Q, Kanellopoulou C, et al. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science. 2015;349(6246):436-40.
28. Sharapova SO, Haapaniemi E, Sakovich IS, Rojas J, Gámez-Díaz L, Mareika YE, et al. Novel LRBA mutation and possible germinal mosaicism in a Slavic family. J Clin Immunol. 2018;38(4):471-474.
29. Liphaus BL, Caramalho I, Rangel-Santos A, Silva CA, Demengeot J, Carneiro-Sampaio MMS. LRBA deficiency: a new genetic cause of monogenic lupus. Ann Rheum Dis. 2020;79(3):427-428.
30. Tesch VK, Abolhassani H, Shadur B, Zobel J, Mareika Y, Sharapova S, et al. Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score. J Allergy Clin Immunol. 2020;145(5):1452-1463.
| Files | ||
| Issue | Vol 4, No 1 (2021) | |
| Section | Review Article | |
| DOI | https://doi.org/10.18502/igj.v4i1.8396 | |
| Keywords | ||
| LRBA Deficiency Joint Involvement Rheumatoid Arthritis Inborn Error of Immunity Juvenile Idiopathic Arthritis | ||
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How to Cite
1.
Rasouli SE, Sharifinejad N, Jamee M, Fallahi M, Hashemi Moghaddam SA, Rekabi M, Daneshmandi Z, Mahdaviani SA, Velayati AA. Joint Involvement in Patients with LPS-Responsive and Beige-Like Anchor Protein (LRBA) Deficiency: A Case Report and Literature Review. Immunol Genet J. 2021;4(1):14-21.
