Increased risk of endocrine autoimmunity in first-degree relatives of patients with autoimmune Addison’s disease

in European Journal of Endocrinology
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  • 1 Department of Endocrinology, Metabolism and Internal Medicine, Poznań University of Medical Sciences, Poznan, Poland
  • 2 Central Laboratory of the Poznan University of Medical Sciences Paediatric Hospital, Poznan, Poland
  • 3 Outpatient Medical Centre Remedium, Pawlowice, Poland
  • 4 Department of Paediatric Diabetes and Obesity, Poznan University of Medical Sciences, Poznan, Poland

Correspondence should be addressed to M Fichna; Email: mfichna@ump.edu.pl
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Objective

Autoimmune conditions tend to cluster in subjects with Addison’s disease (AD) and probably also among their relatives. The aim of the study was to estimate the frequency of the endocrine gland-specific autoantibodies in first-degree relatives of patients with AD.

Methods

Autoantibodies were investigated in 113 family members using RIA and ELISA assays. The control group comprised 143 age-matched volunteers.

Results

Autoimmune diseases were diagnosed in 38.1% relatives. Hashimoto’s thyroiditis was found in 20.3%, Graves’ disease in 8.0%, vitiligo and type 1 diabetes in 3.5%, whereas AD, rheumatoid arthritis and atrophic gastritis with pernicious anaemia in 2.7% each.

All studied antibodies except for islet antigen-2 (P = 0.085) were significantly more frequent in AD relatives than in controls (P < 0.05). Antibodies to 21-hydroxylase were detected in 6.2% relatives, thyroid peroxidase in 28.3%, thyroglobulin in 19.5%, glutamic acid decarboxylase in 8.0%, and zinc transporter-8 in 7.1%. Two and more autoantibodies were detected in 18.6% subjects. Significant gender difference was revealed only for aTPO, more common in female relatives (P = 0.014; OR: 3.16; 95% CI: 1.23–8.12). Circulating autoantibodies were found more frequently in the relatives of affected males (P = 0.008; OR: 3.31; 95% CI: 1.33–8.23), and in family members of patients with polyendocrine autoimmunity (P = 0.009; OR: 3.55; 95% CI: 1.31–9.57).

Conclusions

This study provides evidence of increased susceptibility for the endocrine autoimmunity, especially thyroid disease, in close relatives of patients with AD. Relatives of the male AD patients and of those with autoimmune polyendocrine syndrome are at particular risk and should undergo periodic screening for autoimmune endocrine disorders.

Supplementary Materials

    • Supplementary Table 1. Combinations of multiple endocrine organ-specific autoantibodies detected in serum of 113 first-degree relatives of patients with Addison&#x2019;s disease
    • Supplementary Table 2. Comparison of the frequency of serum autoantibodies against specific adrenal, thyroid and beta cell antigens in first-degree relatives of patients with Addison&#x2019;s disease

 

     European Society of Endocrinology

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  • 1

    Erichsen MM, Lovas K, Skinningsrud B, Wolff AB, Undlien DE, Svartberg J, Fougner KJ, Berg TJ, Bolleslev J & Mella B et al. Clinical, immunological, and genetic features of autoimmune primary adrenal insufficiency: observations from a Norwegian registry. Journal of Clinical Endocrinology and Metabolism 2009 94 48824890. (https://doi.org/10.1210/jc.2009-1368)

    • Search Google Scholar
    • Export Citation
  • 2

    Fichna M, Fichna P, Gryczynska M, Walkowiak J, Zurawek M, Sowiski J. Screening for associated autoimmune disorders in Polish patients with Addison’s disease. Endocrine 2010 37 349360. (https://doi.org/10.1007/s12020-010-9312-x)

    • Search Google Scholar
    • Export Citation
  • 3

    Betterle C, Scarpa R, Garelli S, Morlin L, Lazzarotto F, Presotto F, Coco G, Masiero S, Parolo A & Albergoni MP et al. Addison’s disease: a survey on 633 patients in Padova. European Journal of Endocrinology 2013 169 773784. (https://doi.org/10.1530/EJE-13-0528)

    • Search Google Scholar
    • Export Citation
  • 4

    Neufeld M, Blizzard RM. Polyglandular autoimmune diseases. In Symposium on Autoimmune Aspects of Endocrine Disorders, pp. 357365. Eds Pinchera A, Doniach D, Fenzi GF & Baschieri L. New York: Academic Press, 1980.

    • Search Google Scholar
    • Export Citation
  • 5

    Orlova EM, Sozaeva LS, Kareva MA, Oftedal BE, Wolff ASB, Breivik L, Zakharova EY, Ivanova ON, Kampe O & Dedov II et al. Expanding the phenotypic and genotypic landscape of autoimmune polyendocrine syndrome Type 1. Journal of Clinical Endocrinology and Metabolism 2017 102 35463556. (https://doi.org/10.1210/jc.2017-00139)

    • Search Google Scholar
    • Export Citation
  • 6

    Betterle C, Dal Pra C, Mantero F, Zanchetta R. Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocrine Reviews 2002 23 327364. (https://doi.org/10.1210/edrv.23.3.0466)

    • Search Google Scholar
    • Export Citation
  • 7

    Hemminki K, Li X, Sundquist J, Sundquist K. The epidemiology of Graves’ disease: evidence of a genetic and an environmental contribution. Journal of Autoimmunity 2010 34 J307J313. (https://doi.org/10.1016/j.jaut.2009.11.019)

    • Search Google Scholar
    • Export Citation
  • 8

    Hemminki K, Li X, Sundquist J, Sundquist K. Familial association between type 1 diabetes and other autoimmune and related diseases. Diabetologia 2009 52 18201828. (https://doi.org/10.1007/s00125-009-1427-3)

    • Search Google Scholar
    • Export Citation
  • 9

    Narita T, Oiso N, Fukai K, Kabashima K, Kawada A, Suzuki T. Generalized vitiligo and associated autoimmune diseases in Japanese patients and their families. Allergology International 2011 60 505508. (https://doi.org/10.2332/allergolint.11-OA-0303)

    • Search Google Scholar
    • Export Citation
  • 10

    Spinner MW, Blizzard RM, Gibbs J, Abbey H, Childs B. Familial distributions of organ specific antibodies in the blood of patients with Addison’s disease and hypoparathyroidism and their relatives. Clinical and Experimental Immunology 1969 5 461468.

    • Search Google Scholar
    • Export Citation
  • 11

    White K, Wass J, Elliott A. Inheritance in autoimmune Addison’s: the extended family profile. Endocrine Abstracts 2007 13 P114.

  • 12

    Tromer Y, Dolan LM, Kahaly G, Divers J, D’Agostino RB Jr, Imperatore G, Dabelea D, Marcovina S, Back MH & Pihoker C et al. Genome wide identification of new genes and pathways in patients with both autoimmune thyroiditis and type 1 diabetes. Journal of Autoimmunity 2015 60 3239. (https://doi.org/10.1016/j.jaut.2015.03.006)

    • Search Google Scholar
    • Export Citation
  • 13

    Marquez A, Kerick M, Zhernakova A, Gutierrez-Achury J, Chen WM, Onengut-Gumuscu S, Gonzalez-Alvaro I, Rodriguez-Rodriguez L, Rios-Fernandez R & Gonzalez-Gay MA et al. Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations. Genome Medicine 2018 10 97. (https://doi.org/10.1186/s13073-018-0604-8)

    • Search Google Scholar
    • Export Citation
  • 14

    Jacobson DL, Gange SJ, Rose NR, Graham NM. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clinical Immunology and Immunopathology 1997 84 223243. (https://doi.org/10.1006/clin.1997.4412)

    • Search Google Scholar
    • Export Citation
  • 15

    Cooper GS, Bynum ML, Somers EC. Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. Journal of Autoimmunity 2009 33 197207. (https://doi.org/10.1016/j.jaut.2009.09.008)

    • Search Google Scholar
    • Export Citation
  • 16

    McLeod DS, Cooper DS. The incidence and prevalence of thyroid autoimmunity. Endocrine 2012 42 252265. (https://doi.org/10.1007/s12020-012-9703-2)

    • Search Google Scholar
    • Export Citation
  • 17

    Vanderpump MPJ, Michael W, Tunbridge G. The epidemiology of autoimmune thyroid disease. In Autoimmune Endocrinopathies, pp. 141162. Ed Volpé R. Totowa NJ: Humana Press, 1999.

    • Search Google Scholar
    • Export Citation
  • 18

    Dittmar M, Libich C, Brenzel T, Kahaly GJ. Increased familial clustering of autoimmune thyroid diseases. Hormone and Metabolic Research 2011 43 200204. (https://doi.org/10.1055/s-0031-1271619)

    • Search Google Scholar
    • Export Citation
  • 19

    Walicka M, Chlebus M, Brzozowska M, Śliwczyński A, Jędrzejczyk T, Kania L, Puzianowska-Kuźnicka M, Franek E. Prevalence of diabetes in Poland in the years 2010–2014. Clinical Diabetology 2015 4 232237. (https://doi.org/10.5603/DK.2015.0031)

    • Search Google Scholar
    • Export Citation
  • 20

    Silverberg NB. The epidemiology of vitiligo. Current Dermatology Reports 2015 4 3643. (https://doi.org/10.1007/s13671-014-0098-6)

  • 21

    Batko B, Stajszyk M, Swierkot J, Urbanski K, Raciborski F, Jedrzejewski M, Wiland P. Prevalence and clinical characteristics of rheumatoid arthritis in Poland: a nationwide study. Archives of Medical Science 2019 15 134140. (https://doi.org/10.5114/aoms.2017.71371)

    • Search Google Scholar
    • Export Citation
  • 22

    Meyer G, Neumann K, Badenhoop K, Linder R. Increasing prevalence of Addison’s disease in German females: health insurance data 2008–2012. European Journal of Endocrinology 2014 170 367373. (https://doi.org/10.1530/EJE-13-0756)

    • Search Google Scholar
    • Export Citation
  • 23

    Dalin F, Nordling Eriksson G, Dahlqvist P, Hallgren Å, Wahlberg J, Okwall O, Soderberg S, Ronnelid J, Olcen P & Winqvist O et al. Clinical and immunological characteristics of autoimmune Addison disease: a nationwide Swedish multicenter study. Journal of Clinical Endocrinology and Metabolism 2017 102 379389. (https://doi.org/10.1210/jc.2016-2522)

    • Search Google Scholar
    • Export Citation
  • 24

    Kimpimaki T, Kulmala P, Savola K, Vahasalo P, Reijonen H, Ilonen J, Akerblom HK, Knip M. Disease-associated autoantibodies as surrogate markers of type 1 diabetes in young children at increased genetic risk. Childhood Diabetes in Finland Study Group. Journal of Clinical Endocrinology and Metabolism 2000 85 11261132. (https://doi.org/10.1210/jcem.85.3.6466)

    • Search Google Scholar
    • Export Citation
  • 25

    De Grijse J, Asanghanwa M, Nouthe B, Albrecher N, Goubert P, Vermaulen I, Van Der Meeren S, Decochez K, Weets I & Keymeulen B et al. Predictive power of screening for antibodies against insulinoma-associated protein 2 beta (IA-2beta) and zinc transporter-8 to select first-degree relatives of type 1 diabetic patients with risk of rapid progression to clinical onset of the disease: implications for prevention trials. Diabetologia 2010 53 517524. (https://doi.org/10.1007/s00125-009-1618-y)

    • Search Google Scholar
    • Export Citation
  • 26

    Jonsdottir B, Larsson C, Carlsson A, Forsander G, Ivarsson SA, Lernmark Å, Ludvigsson J, Marcus C, Samuelsson U & Ortqvist E et al. Thyroid and islet autoantibodies predict autoimmune thyroid disease at Type 1 diabetes diagnosis. Journal of Clinical Endocrinology and Metabolism 2017 102 12771285. (https://doi.org/10.1210/jc.2016-2335)

    • Search Google Scholar
    • Export Citation
  • 27

    Betterle C, Volpato M, Rees Smith B, Furmaniak J, Chen S, Zanchetta R, Greggio NA, Pedini B, Boscaro M, Presotto F II. Adrenal cortex and steroid 21-hydroxylase autoantibodies in children with organ-specific autoimmune diseases: markers of high progression to clinical Addison’s disease. Journal of Clinical Endocrinology and Metabolism 1997 82 939942. (https://doi.org/10.1210/jcem.82.3.3849)

    • Search Google Scholar
    • Export Citation
  • 28

    Coco G, Dal Pra C, Presotto F, Albergoni MP, Canova C, Pedini B, Zanchetta R, Chen S, Furmaniak J & Rees Smith B et al. Estimated risk for developing autoimmune Addison’s disease in patients with adrenal cortex autoantibodies. Journal of Clinical Endocrinology and Metabolism 2006 91 16371645. (https://doi.org/10.1210/jc.2005-0860)

    • Search Google Scholar
    • Export Citation
  • 29

    Naletto L, Frigo A, Ceccato F, Sabbadin C, Scarpa R, Presotto F, Dalla Costa M, Faggian D, Plebani M & Censi S et al. The natural history of autoimmune Addison’s disease from the detection of autoantibodies to development of the disease: a long follow-up study on 143 patients. European Journal of Endocrinology 2019 180 223234. (https://doi.org/10.1530/EJE-18-0313)

    • Search Google Scholar
    • Export Citation
  • 30

    Bednarek J, Furmaniak J, Wedlock N, Kiso Y, Baumann-Antczak A, Fowler S, Krishnan H, Craft JA, Rees Smith B. Steroid 21-hydroxylase is a major autoantigen involved in adult onset autoimmune Addison’s disease. FEBS Letters 1992 309 5155. (https://doi.org/10.1016/0014-5793(92)80737-2)

    • Search Google Scholar
    • Export Citation
  • 31

    Colls J, Betterle C, Volpato M, Prentice L, Smith BR, Furmaniak J. Immunoprecipitation assay for autoantibodies to steroid 21-hydroxylase in autoimmune adrenal diseases. Clinical Chemistry 1995 41 375380. (https://doi.org/10.1093/clinchem/41.3.375)

    • Search Google Scholar
    • Export Citation
  • 32

    Betterle C, Coco G, Zanchetta R. Adrenal cortex autoantibodies in subjects with normal adrenal function. Best Practice and Research: Clinical Endocrinology and Metabolism 2005 19 8599. (https://doi.org/10.1016/j.beem.2004.11.008)

    • Search Google Scholar
    • Export Citation
  • 33

    Falorni A, Laureti S, Nikoshokov A, Picchio ML, Hallengren B, Vandewalle CL, Gorus FK, Tortioli C, Luthman H & Brunetti P et al. 21-Hydroxylase autoantibodies in adult patients with endocrine autoimmune diseases are highly specific for Addison’s disease. Belgian Diabetes Registry. Clinical and Experimental Immunology 1997 107 341346. (https://doi.org/10.1111/j.1365-2249.1997.262-ce1153.x)

    • Search Google Scholar
    • Export Citation
  • 34

    Barker JM, Ide A, Hostetler C, Yu L, Miao D, Fain PR, Eisenbarth GS, Gottlieb PA. Endocrine and immunogenetic testing in individuals with type 1 diabetes and 21-hydroxylase autoantibodies: Addison’s disease in a high-risk population. Journal of Clinical Endocrinology and Metabolism 2005 90 128134. (https://doi.org/10.1210/jc.2004-0874)

    • Search Google Scholar
    • Export Citation
  • 35

    Baker PR, Baschal EE, Fain PR, Nanduri P, Triolo TM, Siebert JC, Armstrong TK, Babu SR, Rewers MJ & Gottlieb PA et al. Dominant suppression of Addison’s disease associated with HLA-B15. Journal of Clinical Endocrinology and Metabolism 2011 96 21542162. (https://doi.org/10.1210/jc.2010-2964)

    • Search Google Scholar
    • Export Citation
  • 36

    Baker P, Fain P, Kahles H, Yu L, Hutton J, Wenzlau J, Rewers M, Badenhoop K, Eisenbarth G. Genetic determinants of 21-hydroxylase autoantibodies amongst patients of the Type 1 Diabetes Genetics Consortium. Journal of Clinical Endocrinology and Metabolism 2012 97 E1573E1578. (https://doi.org/10.1210/jc.2011-2824)

    • Search Google Scholar
    • Export Citation
  • 37

    Triolo TM, Baschal EE, Armstrong TK, Toews CS, Fain PR, Rewers MJ, Yu L, Miao D, Eisenbarth GS & Gottlieb PA et al. Homozygosity of the polymorphism MICA5.1 identifies extreme risk of progression to overt adrenal insufficiency among 21-hydroxylase antibody-positive patients with type 1 diabetes. Journal of Clinical Endocrinology and Metabolism 2009 94 45174523. (https://doi.org/10.1210/jc.2009-1308)

    • Search Google Scholar
    • Export Citation
  • 38

    Ragusa F, Fallahi P, Elia G, Gonnella D, Paparo SR, Guysti C, Churilov LP, Ferrari SM, Antonelli A. Hashimotos’ thyroiditis: epidemiology, pathogenesis, clinic and therapy. Best Practice and Research in Clinical Endocrinology and Metabolism 2019 26 101367. (https://doi.org/10.1016/j.beem.2019.101367)

    • Search Google Scholar
    • Export Citation
  • 39

    Lazurova I, Benhatchi K. Autoimmune thyroid diseases and nonorganspecific autoimmunity. Polskie Archiwum Medycyny Wewnetrznej 2012 122 (Supplement 1) 5559. (https://doi.org/10.20452/pamw.1499)

    • Search Google Scholar
    • Export Citation
  • 40

    Winkler C, Jolink M, Knopff A, Kwarteng NA, Achenbach P, Bonifacio E, Ziegler AG. Age, HLA, and sex define a marked risk of organ-specific autoimmunity in first-degree relatives of patients with type 1 diabetes. Diabetes Care 2019 42 16841691. (https://doi.org/10.2337/dc19-0315)

    • Search Google Scholar
    • Export Citation
  • 41

    Hagopian WA, Sanjeevi CB, Kockum I, Landin-Olsson M, Karlsen AE, Sundkvist G, Dahlquist G, Palmer J, Lernmark A. Glutamate decarboxylase-, insulin-, and islet cell-antibodies and HLA typing to detect diabetes in a general population-based study of Swedish children. Journal of Clinical Investigation 1995 95 15051511. (https://doi.org/10.1172/JCI117822)

    • Search Google Scholar
    • Export Citation
  • 42

    Betterle C, Lazzarotto F, Fusari A, Zanchetta R, Bendini S, Pedini B, Moscon A, Presotto F. Pancreatic autoantibodies in Italian patients with newly diagnosed type 1 diabetes mellitus over the age of 20 years. Acta Diabetologica 2006 43 7983. (https://doi.org/10.1007/s00592-006-0217-3)

    • Search Google Scholar
    • Export Citation
  • 43

    Rogowicz-Frontczak A, Zozulinska-Ziolkiewicz D, Litwinowicz M, Niedziwiecki P, Wyka K, Wierusz-Wysocka B. Are zinc transporter type 8 antibodies a marker of autoimmune thyroiditis in non-obese adults with new-onset diabetes? European Journal of Endocrinology 2014 170 651658. (https://doi.org/10.1530/EJE-13-0901)

    • Search Google Scholar
    • Export Citation
  • 44

    Karagzuel G, Simsek S, Deger O, Okten A. Screening of diabetes, thyroid, and celiac diseases-related autoantibodies in a sample of Turkish children with type 1 diabetes and their siblings. Diabetes Research and Clinical Practice 2008 80 238243. (https://doi.org/10.1016/j.diabres.2007.12.007)

    • Search Google Scholar
    • Export Citation
  • 45

    Bingley PJ, Boulware DC, Krischer JP & Type 1 Diabetes TrialNet Study Group. The implications of autoantibodies to a single islet antygen in relatives with normal glucose tolerance: development of other autoantibodies and progression to type 1 diabetes. Diabetologia 2016 59 542549. (https://doi.org/10.1007/s00125-015-3830-2)

    • Search Google Scholar
    • Export Citation
  • 46

    Fichna M, Rogowicz-Frontczak A, Zurawek M, Fichna P, Gryczynska M, Zozulinska-Ziolkiewicz D, Ruchala M. Positive autoantibodies to ZnT8 indicate elevated risk for additional autoimmune conditions in patients with Addison’s disease. Endocrine 2016 53 249257. (https://doi.org/10.1007/s12020-016-0916-7)

    • Search Google Scholar
    • Export Citation
  • 47

    Wenzlau JM, Juhl K, Yu L, Moua O, Sarkar SA, Gottlieb P, Rewers M, Eisenbarth GS, Jensen J & Davidson HW et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. PNAS 2007 104 1704017045. (https://doi.org/10.1073/pnas.0705894104)

    • Search Google Scholar
    • Export Citation
  • 48

    Gorus FK, Balti EV, Vermeulen I, Demeester S, Van Dalem A, Costa O, Dorchy H, Tenoutasse S, Mouraux T & De Block C et al. Screening for insulinoma antigen 2 and zinc transporter 8 autoantibodies: a cost-effective and age-independent strategy to identify rapid progressors to clinical onset among relatives of type 1 diabetic patients. Clinical and Experimental Immunology 2013 171 8290. (https://doi.org/10.1111/j.1365-2249.2012.04675.x)

    • Search Google Scholar
    • Export Citation
  • 49

    Incani M, Serafini C, Satta C, Perra L, Scano F, Frongia P, Ricciardi R, Ripoli C, Soro M & Strazzera A et al. High prevalence of diabetes-specific autoimmunity in first-degree relatives of Sardinian patients with type 1 diabetes. Diabetes/Metabolism Research and Reviews 2017 33 e2864. (https://doi.org/10.1002/dmrr.2864)

    • Search Google Scholar
    • Export Citation
  • 50

    Irvine WJ, Stewart AG, Scarth L. A clinical and immunological study of adrenocortical insufficiency (Addison’s disease). Clinical and Experimental Immunology 1967 2 3170.

    • Search Google Scholar
    • Export Citation
  • 51

    Ji J, Sundquist J, Sundquist K. Gender-specific incidence of autoimmune diseases from national registers. Journal of Autoimmunity 2016 69 102106. (https://doi.org/10.1016/j.jaut.2016.03.003)

    • Search Google Scholar
    • Export Citation
  • 52

    Harjutsalo V, Reunanen A, Tuomilehto J. Differential transmission of type 1 diabetes from diabetic fathers and mothers to their offspring. Diabetes 2006 55 15171524. (https://doi.org/10.2337/db05-1296)

    • Search Google Scholar
    • Export Citation
  • 53

    Zhernakova A, Withoff S, Wijmenga C. Clinical implications of shared genetics and pathogenesis in autoimmune diseases. Nature Reviews: Endocrinology 2013 9 646659. (https://doi.org/10.1038/nrendo.2013.161)

    • Search Google Scholar
    • Export Citation
  • 54

    Mitchell AL, Pearce SH. Autoimmune Addison’s disease: pathophysiology and genetic complexity. Nature Reviews in Endocrinology 2012 8 306316. (https://doi.org/10.1038/nrendo.2011.245)

    • Search Google Scholar
    • Export Citation
  • 55

    Pazderska A, Oftedal BE, Napier CM, Ainsworth HF, Husebye ES, Cordell HJ, Pearce SH, Michell AL. A variant in the BACH2 gene is associated with susceptibility to autoimmune Addison’s disease in humans. Journal of Clinical Endocrinology and Metabolism 2016 101 38653869. (https://doi.org/10.1210/jc.2016-2368)

    • Search Google Scholar
    • Export Citation
  • 56

    Skov J, Hoijer J, Magnusson PKE, Ludvigsson JF, Kampe O, Bensing S. Heritability of Addison’s disease and prevalence of associated autoimmunity in a cohort of 112,100 Swedish twins. Endocrine 2017 58 521527. (https://doi.org/10.1007/s12020-017-1441-z)

    • Search Google Scholar
    • Export Citation
  • 57

    Weinstock C, Matheis N, Barkia S, Haager MC, Janson A, Markovic A, Bux J, Kahaly GJ. Autoimmune polyglandular syndrome type 2 shows the same HLA class II pattern as type 1 diabetes. Tissue Antigens 2011 77 317324. (https://doi.org/10.1111/j.1399-0039.2011.01634.x)

    • Search Google Scholar
    • Export Citation
  • 58

    Flesch BK, Matheis N, Alt T, Weinstock C, Bux J, Kahaly GJ. HLA class II haplotypes differentiate between the adult autoimmune polyglandular syndrome types II and III. Journal of Clinical Endocrinology and Metabolism 2014 99 E177E182. (https://doi.org/10.1210/jc.2013-2852)

    • Search Google Scholar
    • Export Citation
  • 59

    Houcken J, Degenhart C, Bender K, Konig J, Frommer L, Kahaly GJ. PTPN22 and CTLA-4 polymorphisms are associated with polyglandular autoimmunity. Journal of Clinical Endocrinology and Metabolism 2018 103 19771984. (https://doi.org/10.1210/jc.2017-02577)

    • Search Google Scholar
    • Export Citation