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Relationship between human leukocyte antigen (HLA) alleles and pediatric autoimmune neuropsychiatric disorders associated with Streptococcal infections (PANDAS)

Year 2019, Volume: 44 Issue: 1, 52 - 58, 31.03.2019
https://doi.org/10.17826/cumj.426378

Abstract

Purpose: The aim of this study is to examine the relationship between Pediatric autoimmune neuropsychiatric disorders associated with Streptococcal infections (PANDAS) and Human Leukocyte Antigen (HLA) alleles. 

Materials and Methods: HLA alleles of 41 children patients, whom are diagnosed with rapid onset of obsessive compulsive disorder (OCD), and 88 healthy children are analyzed by using PCR. Results are evaluated by using univariate and multivariate logistic regression analysis.

Results: DRB8, DRB5.2 and DQ5 alleles increase risk of disease while A1, B18 and B35 alleles decrease risk of disease. 

Conclusion: Findings of this study will help researchers to examine related genes in PANDAS and the effects of gene products on development of the disease. Presentation of exogenic antigens to T-helper cells by HLA class II loci is determined in different autoimmune diseases. Similarity of these findings with PANDAS etiology and risk increasing alleles found in this study being HLA class II is remarkable.


References

  • Moretti G, Pasquini M, Mandarelli G, Tarsitani L, Biondi M. What every psychiatrist should know about PANDAS: a review. Clin Pract Epidemiol Ment Health. 2008; 4:13.
  • de Oliveira SK, Pelajo CF. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS): a Controversial Diagnosis. Curr Infect Dis Rep. 2010; 12:103-9.
  • Boileau B. A review of obsessive-compulsive disorder in children and adolescents. Dialogues Clin Neurosci. 2011; 13:401-11.
  • Pichichero ME. The PANDAS syndrome. Adv Exp Med Biol. 2009; 634:205-16.
  • Murphy TK, Kurlan R, Leckman J. The immunobiology of Tourette's disorder, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus, and related disorders: a way forward. J Child Adolesc Psychopharmacol. 2010; 20:317-31.
  • Shulman ST. Pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS): update. Curr Opin Pediatr. 2009; 21:127-30.
  • Asbahr FR, Negrao AB, Gentil V, Zanetta DMT, da Paz JA, Marques-Dias MJ et al. Obsessive-compulsive and related symptoms in children and adolescents with rheumatic fever with and without chorea: A prospective 6-month study. Am J Psychiatry. 1998; 155:1122-4.
  • Cusick MF, Libbey JE, Fujinami RS. Molecular Mimicry as a Mechanism of Autoimmune Disease. Clin Rev Allergy Immunol. 2012; 42:102-11.
  • Leverkus M, McLellan AD, Heldmann M, Eggert AO, Brocker EB, Koch N et al. MHC class II-mediated apoptosis in dendritic cells: a role for membrane-associated and mitochondrial signaling pathways. Int Immunol. 2003; 15:993-1006.
  • Gough SCL, Simmonds MJ. The HLA region and autoimmune disease: Associations and mechanisms of action. Curr Genomics. 2007; 8:453-65.
  • Swedo SE, Leonard HL. Childhood Movement-Disorders and Obsessive-Compulsive Disorder. J Clin Psychiatr. 1994; 55:32-7.
  • Ozcan ME. Human leukocyte antigen DR1 in Japanese and Turkish patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2006; 30:423-8.
  • Wright P, Nimgaonkar VL, Donaldson PT, Murray RM. Schizophrenia and HLA: a review. Schizophr Res. 2001; 47:1-12.
  • Allen AJ, Leonard HL, Swedo SE. Case study: a new infection-triggered, autoimmune subtype of pediatric OCD and Tourette's syndrome. J Am Acad Child Adolesc Psychiatry. 1995; 34:307-11.
  • Garvey MA, Giedd J, Swedo SE. PANDAS: the search for environmental triggers of pediatric neuropsychiatric disorders. Lessons from rheumatic fever. J Child Neurol. 1998; 13:413-23.
  • Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry. 1998; 155:264-71.
  • Swedo SE, Leonard HL, Rapoport JL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup: separating fact from fiction. Pediatrics. 2004; 113:907-11.
  • Pavone P, Parano E, Rizzo R, Trifiletti RR. Autoimmune neuropsychiatric disorders associated with streptococcal infection: Sydenham chorea, PANDAS, and PANDAS variants. J Child Neurol. 2006; 21:727-36.
  • van Toorn R, Weyers HH, Schoeman JF. Distinguishing PANDAS from Sydenham's chorea: case report and review of the literature. Eur J Paediatr Neurol. 2004; 8:211-6.
  • Murphy TK, Goodman WK, Fudge MW, Williams RC, Jr., Ayoub EM, Dalal M et al. B lymphocyte antigen D8/17: a peripheral marker for childhood-onset obsessive-compulsive disorder and Tourette's syndrome? Am J Psychiatry. 1997; 154:402-7.
  • Simmonds MJ, Gough SCL. Genetic insights into disease mechanisms of autoimmunity. Br Med Bull. 2004; 71:93-113.
  • Zai G, Bezchlibnyk YB, Richter MA, Arnold P, Burroughs E, Barr CL et al. Myelin oligodendrocyte glycoprotein (MOG) gene is associated with obsessive-compulsive disorder. American Journal of Medical Genetics Part B-Neuropsychiatric Genetics. 2004; 129b:64-8.
  • Villadangos JA. Presentation of antigens by MHC class II molecules: getting the most out of them. Mol Immunol. 2001; 38:329-46.
  • Gromme M, Neefjes J. Antigen degradation or presentation by MHC class I molecules via classical and non-classical pathways. Mol Immunol. 2002; 39:181-202.
  • Parham P. Presentation of HLA class I-derived peptides: potential involvement in allorecognition and HLA-B27-associated arthritis. Immunol Rev. 1996; 154:137-54.
  • Singal DP, Blajchman MA. Histocompatibility (HL-A) antigens, lymphocytotoxic antibodies and tissue antibodies in patients with diabetes mellitus. Diabetes. 1973; 22:429-32.
  • Cudworth AG, Woodrow JC. HL-A system and diabetes mellitus. Diabetes. 1975; 24:345-9.
  • Thorsby E, Lie BA. HLA associated genetic predisposition to autoimmune diseases: Genes involved and possible mechanisms. Transpl Immunol. 2005; 14:175-82.
  • Zanelli E, Breedveld FC, de Vries RR. HLA association with autoimmune disease: a failure to protect? Rheumatology (Oxford). 2000; 39:1060-6.

Streptokok enfeksiyonu ile ilişkili pediatrik otoimmün nöropsikiyatrik hastalık (PANDAS) ile insan lököksit antijen (HLA) ilişkisi

Year 2019, Volume: 44 Issue: 1, 52 - 58, 31.03.2019
https://doi.org/10.17826/cumj.426378

Abstract

Amaç: Bu çalışmada Streptokok enfeksiyonları ile ilişkili pediyatrik otoimmün nöropsikiyatrik bozukluklar (PANDAS) ve İnsan Lökosit Antijen (HLA) allelleri arasındaki ilişkinin incelenmesi amaçlanmıştır.

Gereç ve Yöntem: Ani başlangıçlı obsesif kompulsif bozukluğu (OKB) olan 41 çocuk hastanın ve 88 sağlıklı çocuğun HLA alelleri PCR kullanılarak analiz edildi. Sonuçlar univariate ve multivariate lojistik regresyon analizi kullanılarak değerlendirildi.

Bulgular: A1, B18 ve B35 allellerinin hastalık riskini azaltırken, DRB8, DRB5.2 ve DQ5 allellerinin hastalık riskini artırdığı saptanmıştır.

Sonuç: Bu çalışmanın bulguları, araştırmacıların PANDAS'taki ilgili genleri ve gen ürünlerinin hastalığın gelişimine olan etkilerini incelemelerine yardımcı olacaktır. HLA sınıf II lokusları tarafından T-yardımcı hücrelere ekzojenik antijenlerin tanıtımı farklı otoimmün hastalıklarda belirlenmiştir. Bu bulguların PANDAS etiyolojisi ile benzerliği ve bu çalışmada bulunan hastalık riskini artıran allellerin, HLA sınıf II’de bulunması dikkat çekicidir.


References

  • Moretti G, Pasquini M, Mandarelli G, Tarsitani L, Biondi M. What every psychiatrist should know about PANDAS: a review. Clin Pract Epidemiol Ment Health. 2008; 4:13.
  • de Oliveira SK, Pelajo CF. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS): a Controversial Diagnosis. Curr Infect Dis Rep. 2010; 12:103-9.
  • Boileau B. A review of obsessive-compulsive disorder in children and adolescents. Dialogues Clin Neurosci. 2011; 13:401-11.
  • Pichichero ME. The PANDAS syndrome. Adv Exp Med Biol. 2009; 634:205-16.
  • Murphy TK, Kurlan R, Leckman J. The immunobiology of Tourette's disorder, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus, and related disorders: a way forward. J Child Adolesc Psychopharmacol. 2010; 20:317-31.
  • Shulman ST. Pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS): update. Curr Opin Pediatr. 2009; 21:127-30.
  • Asbahr FR, Negrao AB, Gentil V, Zanetta DMT, da Paz JA, Marques-Dias MJ et al. Obsessive-compulsive and related symptoms in children and adolescents with rheumatic fever with and without chorea: A prospective 6-month study. Am J Psychiatry. 1998; 155:1122-4.
  • Cusick MF, Libbey JE, Fujinami RS. Molecular Mimicry as a Mechanism of Autoimmune Disease. Clin Rev Allergy Immunol. 2012; 42:102-11.
  • Leverkus M, McLellan AD, Heldmann M, Eggert AO, Brocker EB, Koch N et al. MHC class II-mediated apoptosis in dendritic cells: a role for membrane-associated and mitochondrial signaling pathways. Int Immunol. 2003; 15:993-1006.
  • Gough SCL, Simmonds MJ. The HLA region and autoimmune disease: Associations and mechanisms of action. Curr Genomics. 2007; 8:453-65.
  • Swedo SE, Leonard HL. Childhood Movement-Disorders and Obsessive-Compulsive Disorder. J Clin Psychiatr. 1994; 55:32-7.
  • Ozcan ME. Human leukocyte antigen DR1 in Japanese and Turkish patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2006; 30:423-8.
  • Wright P, Nimgaonkar VL, Donaldson PT, Murray RM. Schizophrenia and HLA: a review. Schizophr Res. 2001; 47:1-12.
  • Allen AJ, Leonard HL, Swedo SE. Case study: a new infection-triggered, autoimmune subtype of pediatric OCD and Tourette's syndrome. J Am Acad Child Adolesc Psychiatry. 1995; 34:307-11.
  • Garvey MA, Giedd J, Swedo SE. PANDAS: the search for environmental triggers of pediatric neuropsychiatric disorders. Lessons from rheumatic fever. J Child Neurol. 1998; 13:413-23.
  • Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry. 1998; 155:264-71.
  • Swedo SE, Leonard HL, Rapoport JL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup: separating fact from fiction. Pediatrics. 2004; 113:907-11.
  • Pavone P, Parano E, Rizzo R, Trifiletti RR. Autoimmune neuropsychiatric disorders associated with streptococcal infection: Sydenham chorea, PANDAS, and PANDAS variants. J Child Neurol. 2006; 21:727-36.
  • van Toorn R, Weyers HH, Schoeman JF. Distinguishing PANDAS from Sydenham's chorea: case report and review of the literature. Eur J Paediatr Neurol. 2004; 8:211-6.
  • Murphy TK, Goodman WK, Fudge MW, Williams RC, Jr., Ayoub EM, Dalal M et al. B lymphocyte antigen D8/17: a peripheral marker for childhood-onset obsessive-compulsive disorder and Tourette's syndrome? Am J Psychiatry. 1997; 154:402-7.
  • Simmonds MJ, Gough SCL. Genetic insights into disease mechanisms of autoimmunity. Br Med Bull. 2004; 71:93-113.
  • Zai G, Bezchlibnyk YB, Richter MA, Arnold P, Burroughs E, Barr CL et al. Myelin oligodendrocyte glycoprotein (MOG) gene is associated with obsessive-compulsive disorder. American Journal of Medical Genetics Part B-Neuropsychiatric Genetics. 2004; 129b:64-8.
  • Villadangos JA. Presentation of antigens by MHC class II molecules: getting the most out of them. Mol Immunol. 2001; 38:329-46.
  • Gromme M, Neefjes J. Antigen degradation or presentation by MHC class I molecules via classical and non-classical pathways. Mol Immunol. 2002; 39:181-202.
  • Parham P. Presentation of HLA class I-derived peptides: potential involvement in allorecognition and HLA-B27-associated arthritis. Immunol Rev. 1996; 154:137-54.
  • Singal DP, Blajchman MA. Histocompatibility (HL-A) antigens, lymphocytotoxic antibodies and tissue antibodies in patients with diabetes mellitus. Diabetes. 1973; 22:429-32.
  • Cudworth AG, Woodrow JC. HL-A system and diabetes mellitus. Diabetes. 1975; 24:345-9.
  • Thorsby E, Lie BA. HLA associated genetic predisposition to autoimmune diseases: Genes involved and possible mechanisms. Transpl Immunol. 2005; 14:175-82.
  • Zanelli E, Breedveld FC, de Vries RR. HLA association with autoimmune disease: a failure to protect? Rheumatology (Oxford). 2000; 39:1060-6.
There are 29 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research
Authors

Gökhan Karacaoğlan This is me 0000-0003-0774-2501

Ümit Lüleyap 0000-0001-8759-1381

Ayşegül Yolga Tahiroğlu 0000-0002-3039-2864

Perçin Pazarcı This is me 0000-0002-3708-0054

Akgün Yaman This is me 0000-0003-3309-3074

Salih Çetiner 0000-0002-5464-0340

Yaşar Sertdemir This is me 0000-0003-4455-3590

Doğa Lüleyap This is me 0000-0002-8201-0928

Publication Date March 31, 2019
Acceptance Date August 6, 2018
Published in Issue Year 2019 Volume: 44 Issue: 1

Cite

MLA Karacaoğlan, Gökhan et al. “Relationship Between Human Leukocyte Antigen (HLA) Alleles and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS)”. Cukurova Medical Journal, vol. 44, no. 1, 2019, pp. 52-58, doi:10.17826/cumj.426378.