The Coincidence of Newly Diagnosed Type 1 Diabetes Mellitus with IgM Antibody Positivity to Enteroviruses and Respiratory Tract Viruses

Murat Karaoglan, Fahriye Eksi, Murat Karaoglan, Fahriye Eksi

Abstract

Objective: Viruses trigger and promote islet cell destruction and cause type 1 diabetes mellitus (T1DM). However, the existence of a cause-and-effect relationship is under debate. The aim of this study is to investigate the sero-epidemiological and molecular evidence on enteroviruses and respiratory viruses in patients with newly diagnosed T1DM during the cold season.

Design: Forty children newly diagnosed with T1DM and 30 healthy children who presented to the clinic over the course of a year were included in the study. The IgM antibodies against enteroviruses and respiratory viruses were studied using the indirect immunofluorescence assay (IFA) test, and no CBV4-specific RNA was detected in the children. The onset times of T1DM were classified into fall-winter and spring-summer seasons and separated into cold, moderate, or warm months in terms of temperature.

Results: The percentages of viral IgM antibodies against most common viruses were detected in the patients as follows: influenza B (IVB) (70%), echovirus 7 (ECHO7) (45%), parainfluenza virus 4 (PIV4) (40%), coxsackievirus A7 (CAV7) (27.5%), and H3N2 (22.5%). Compared with the control group, the above viruses had a significant association with T1DM (p ≤ 0.001, p ≤ 0.001, p = 0.035, p = 0.003, and p = 0.023, resp.). CBV4-specific RNA was not detected in any serum. A total of 75% and 95% patients were diagnosed with T1DM in the fall-winter seasons and cold-moderate months, respectively.

Conclusion: Our study demonstrates the significant association between T1DM and the presence of IgM antibodies against IVB, ECHO7, PIV4, CAV7, and H3N2, and the majority of newly diagnosed T1DM appeared in the fall-winter season. It suggests that enteroviruses and respiratory viruses, in addition to seasonal variation, could play a role in the etiopathogenesis and clinical onset of T1DM.

Figures

Figure 1
Figure 1
The distribution of patients newly diagnosed with T1DM (n) in each season.
Figure 2
Figure 2
The distribution patients newly diagnosed with T1DM (n) in each month group.

References

    1. Hiltunen M., Hyöty H., Knip M., et al. Islet cell antibody seroconversion in children is temporally associated with enterovirus infections. The Journal of Infectious Diseases. 1997;175(3):554–560. doi: 10.1093/infdis/175.3.554.
    1. Hober D., Sane F., Jaïdane H., Riedweg K., Goffard A., Desailloud R. Immunology in the clinic review series; focus on type 1 diabetes and viruses: role of antibodies enhancing the infection with coxsackievirus-B in the pathogenesis of type 1 diabetes. Clinical & Experimental Immunology. 2012;168(1):47–51. doi: 10.1111/j.1365-2249.2011.04559.x.
    1. Stene L. C., Rewers M. Immunology in the clinic review series; focus on type 1 diabetes and viruses: the enterovirus link to type 1 diabetes: critical review of human studies. Clinical & Experimental Immunology. 2012;168(1):12–23. doi: 10.1111/j.1365-2249.2011.04555.x.
    1. Valdés C., Unanue N., Hernández M., et al. Is there a link between influenza and type I diabetes? Increased incidence of TID during the pandemic H1N1 influenza of 2009 in Chile. Pediatric endocrinology reviews. 2013;11(2):161–166.
    1. Capua I., Mercalli A., Pizzuto M. S., et al. Influenza A viruses grow in human pancreatic cells and cause pancreatitis and diabetes in an animal model. Journal of Virology. 2013;87(1):597–610. doi: 10.1128/JVI.00714-12.
    1. Grieco F. A., Sebastiani G., Spagnuolo I., Patti A., Dotta F. Immunology in the clinic review series; focus on type 1diabetes and viruses: how viral infections modulate beta cell function. Clinical & Experimental Immunology. 2012;168(1):24–29. doi: 10.1111/j.1365-2249.2011.04556.x.
    1. Eringsmark R. S., Lernmark A. The environment and the origins of islet autoimmunity and Type 1 diabetes. Diabetic Medicine. 2013;30(2):155–160. doi: 10.1111/dme.12099.
    1. Patterson C. C., Gyürüs E., Rosenbaueretal J. Seasonal variation in month of diagnosis in children with type 1 diabetes registered in 23 European centers during 1989-2008: little short-term influence of sunshine hours or average temperature. Pediatric Diabetes. 2015;16(8):573–580. doi: 10.1111/pedi.12227.
    1. Kalliora M. I., Vazeou A., Delis D., Bozas E., Thymelli I., Bartsocas C. S. Seasonal variation of type 1 diabetes mellitus diagnosis in Greek children. Hormones. 2011;10(1):67–71. doi: 10.14310/horm.2002.1294.
    1. Piccini B., Toni S., Lenzi L., Guasti M., Barni F., De Martino M. Type 1 diabetes onset and pandemic influenza A (H1N1) International Journal of Immunopathology and Pharmacology. 2012;25(2):547–549. doi: 10.1177/039463201202500228.
    1. Schneider D. A., von Herrath M. G. Viruses and type 1 diabetes: a dynamic labile equilibrium. Diabetes Management. 2013;3(3):217–223. doi: 10.2217/dmt.13.17.
    1. Waner J. L. Mixed viral infections: detection and management. Clinical Microbiology Reviews. 1994;7(2):143–151. doi: 10.1128/CMR.7.2.143.
    1. OutiVaarala M., Atkinson A., Neu J. The “perfect storm” for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability, and mucosal immunity. Diabetes. 2008;57(10):2555–2562. doi: 10.2337/db08-0331.
    1. Vaarala O. Gut microbiota and type 1 diabetes. The Review of Diabetic Studies. 2012;9(4):251–259. doi: 10.1900/RDS.2012.9.251.
    1. Salvatoni A., Baj A., Bianchi G., Federico G., Colombo M., Toniolo A. Intrafamilial spread of enterovirus infections at the clinical onset of type 1 diabetes. Pediatric Diabetes. 2013;14(6):407–416. doi: 10.1111/pedi.12056.
    1. Öztürk M. Z., Çetinkaya G., Aydın S. Climate types of Turkey according to Köppen-Geiger climate classification. Journal of Geography. 2017;35:17–27.
    1. Çekin Y., Özkaya E., Gülkesen H., Akçurin S., Çolak D. Investigation of enterovirus infections, autoimmune factors and HLA genotypes in patients with T1DM. Minerva Endocrinol. 2014;39(1):67–74.
    1. Canas C. A., Canas F. The biological significance of evolution in autoimmune phenomena. Autoimmune Diseases. 2012;2012:12. doi: 10.1155/2012/784315.784315
    1. Dunne D. W., Cooke A. A worm’s eye view of the immune system: consequences for evolution of human autoimmune disease. Nature Reviews Immunology. 2005;5(5):420–426. doi: 10.1038/nri1601.
    1. Lind K., Hühn M. H., Flodström-Tullberg M. Immunology in the clinic review series; focus on type 1 diabetes and viruses: the innate immune response to enteroviruses and its possible role in regulating type 1 diabetes. Clinical & Experimental Immunology. 2012;168(1):30–38. doi: 10.1111/j.1365-2249.2011.04557.x.
    1. Simoni Y., Diana J., Ghazarian L., Beaudoin L., Lehuen A. Therapeutic manipulation of natural killer (NK) T cells in autoimmunity: are we close to reality? Clinical & Experimental Immunology. 2013;171(1):8–19. doi: 10.1111/j.1365-2249.2012.04625.x.
    1. Zipris D. Epidemiology of type 1 diabetes and what animal models teach us about the role of viruses in disease mechanisms. Clinical Immunology. 2009;131(1):11–23. doi: 10.1016/j.clim.2008.12.011.
    1. Atkinson M. A., Eisenbarth G. S. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. The Lancet. 2001;358(9277):221–229. doi: 10.1016/S0140-6736(01)05415-0.

Source: PubMed

3
Suscribir