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Antibodies against NALP5 and it’s role in hypoparathyroidism in autoimmune polyglandular syndrome type 1

https://doi.org/10.14341/probl201662225-30

Abstract

Hypoparathyroidism is one of major components of autoimmune polyglandular syndrome type 1 (APS type 1) with a prevalence 73—83%. The protein NALP5 has been described previously as an antigen of parathyroid glands. 

Aim — to investigate antibodies against NALP5 in patients with APS type 1. 

Material and methods. Seventy nine patients with APS type 1 were included in the study. Radio-immune assay was used for detecting antibodies against NALP5. 

Results. The correlation between hypoparathyroidism and high levels of antibodies against NALP5 was found (p<0.001). Sensitivity of the method was 69,4%, specificity — 83,3%, positive predictive value — 93,5%, negative predictive value — 44,1%. Correlations between other components of the disease and high levels of the antibodies were not found. 

ConclusionsWe found a positive correlation between antibodies against NALP5 and hypoparathyroidism in APS type 1 patients. We did not find correlations between antibodies against NALP5 and other components of APS type 1.

About the Authors

Leila S. Sozaeva
Endocrinology Research Centre
Russian Federation
MD
Competing Interests: нет конфликта интересов


Elizaveta M. Orlova
Endocrinology Research Centre; I.M. Sechenov First Moscow State Medical University
Russian Federation
MD, PhD, Leading researcher
Competing Interests: нет конфликта интересов


Bergithe Oftedal
University of Bergen
Norway
PhD, post doctoral fellow (University of Bergen, N-5020 Bergen, Norway).


Maria A. Kareva
Endocrinology Research Centre
Russian Federation

Competing Interests: нет конфликта интересов


Valentina A. Peterkova
Endocrinology Research Centre; I.M. Sechenov First Moscow State Medical University
Russian Federation
MD, PhD, Professor, Head of the Pediaric endocrinology department


Ivan I. Dedov
Endocrinology Research Centre
Russian Federation
MD, PhD, Professor, Academician of Russian academy of sciences, director of Endocrinology Research Centre


Eystein Sverre Husbye
University of Bergen
Norway
MD, PhD, Professor, head of the Endocrinology group, University of Bergen, N-5020 Bergen, Norway


References

1. Finnish-German AC. An autoimmune disease, apeced, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat Genet. 1997;17(4):399-403. doi: 10.1038/Ng1297-399.

2. Anderson MS, Venanzi ES, Chen Z, et al. The cellular mechanism of Aire control of T-cell tolerance. Immunity. 2005;23(2):227-239. doi: 10.1016/J.Immuni.2005.07.005.

3. Orlova EM, Bukina AM, Kuznetsova ES, et al. Autoimmune polyglandular syndrome type 1 in Russian patients: clinical variants and autoimmune regulator mutations. Horm Res Paediatr. 2010;73(6):449-457. doi: 10.1159/000313585.

4. Ahonen P, Myllarniemi S, Sipila I, Perheentupa J. Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med. 1990;322(26):1829-1836. doi: 10.1056/Nejm199006283222601.

5. Perheentupa J. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Horm Metab Res. 1996;28(7):353-356. doi: 10.1055/S-2007-979814.

6. Wolff AS, Erichsen MM, Meager A, et al. Autoimmune polyendocrine syndrome type 1 in Norway: phenotypic variation, autoantibodies, and novel mutations in the autoimmune regulator gene. J Clin Endocrinol Metab. 2007;92(2):595-603. doi: 10.1210/Jc.2006-1873.

7. Soderbergh A, Myhre AG, Ekwall O, et al. Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type 1. J Clin Endocrinol Metab. 2004;89(2):557-562. doi: 10.1210/Jc.2003-030279.

8. Meloni A, Furcas M, Cetani F, et al. Autoantibodies against type 1 interferons as an additional diagnostic criterion for autoimmune polyendocrine syndrome type 1. J Clin Endocrinol Metab. 2008;93(11):4389-4397. doi: 10.1210/jc.2008-0935.

9. Gylling M, Kaariainen E, Vaisanen R, et al. The hypoparathyroidism of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protective effect of male sex. J Clin Endocrinol Metab. 2003;88(10):4602-4608. doi: 10.1210/jc.2003-030700.

10. Alimohammadi M, Bjorklund P, Hallgren A, et al. Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen. N Engl J Med. 2008;358(10):1018-1028. doi: 10.1056/NEJMoa0706487.

11. Brozzetti A, Alimohammadi M, Morelli S, et al. Autoantibody response against NALP5/MATER in primary ovarian insufficiency and in autoimmune addison’s disease. J Clin Endocrinol metab. 2015;100(5):1941-1948. doi: 10.1210/jc.2014-3571.

12. Meloni A, Willcox N, Meager A, et al. Autoimmune polyendocrine syndrome type 1: an extensive longitudinal study in sardinian patients. J clin endocrinol metab. 2012;97(4):1114-1124. doi: 10.1210/jc.2011-2461.

13. Reato G, Morlin L, Chen S, et al. Premature ovarian failure in patients with autoimmune addison’s disease: clinical, genetic, and immunological evaluation. J Clin Endocrinol Metab. 2011;96(8):e1255-1261. doi: 10.1210/jc.2011-0414.

14. Kemp EH, Habibullah M, Kluger N, et al. Prevalence and clinical associations of calcium-sensing receptor and NALP5 autoantibodies in finnish apeced patients. J Clin Endocrinol Metab. 2014;99(3):1064-1071. doi: 10.1210/jc.2013-3723.


Review

For citations:


Sozaeva L.S., Orlova E.M., Oftedal B., Kareva M.A., Peterkova V.A., Dedov I.I., Husbye E.S. Antibodies against NALP5 and it’s role in hypoparathyroidism in autoimmune polyglandular syndrome type 1. Problems of Endocrinology. 2016;62(2):25-30. https://doi.org/10.14341/probl201662225-30

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ISSN 0375-9660 (Print)
ISSN 2308-1430 (Online)