Peripheral immunity in patients with autoimmune endocrine diseases and the influence of physiological adaptions during pregnancy

• Type 1 diabetes (T1D), Hashimoto’s thyroiditis (HT), Graves’ disease (GD), and autoimmune Addison’s disease (AD) appear to share immunogenetic mechanisms. This idea is not novel, as “autoimmune tautology” is an established concept. An issue with previous studies is that no or few simultaneous comparisons between these autoimmune endocrine diseases have been made. Due to methodological limitations, immune deviations associated with these diseases have also been examined for a limited number of immune cell lineages and analytes. High-dimensional single-cell mass cytometry was thus employed to phenotypically characterise all peripheral CD45+ cell lineages, whilst immune-related proteins in plasma and cell supernatants were analysed by proximity extension assay. Patients with new-onset T1D, HT, and AD had altered frequencies of distinct clusters within antigen-presenting and cytotoxic cell lineages. Importantly, previously unreported alterations of rare cell subsets from patients with HT and AD were identified. The systemic immunoprofile of patients with autoimmune endocrine diseases was in general similar. However, an increased abundance of CDCP1 and SLAMF1 in plasma from patients with T1D, HT, and GD might reflect a higher degree of inflammation and lymphocyte activation.Pregnancy in healthy women entails two important features: 1) an increase in fractional β-cell area and 2) peripheral immunomodulation. The effects of pregnancy on T1D remain nevertheless equivocal, as there are conflicting results on β-cell function and longitudinal analyses on peripheral immunity are lacking. β-cell function and the plasma proteome in pregnant women with long-standing T1D (L-T1D) were therefore examined during three occasions: 1) first trimester, 2) third trimester, and 3) two months postpartum. An oral glucose tolerance test was performed to measure both fasting and stimulated C-peptide concentrations in plasma. Plasma proteins related to cell regulatory and immunological processes were analysed by proximity extension assay. Glucose-induced insulin secretion was regained in pregnant women with L-T1D, which decreased slowly after parturition. The plasma proteome was dynamic during gestation, although few analytes were functionally linked. A recovered β-cell function might be related to elevated plasma levels of prolactin, prokineticin-1, or glucagon. Moreover, reduced plasma levels of proteins related to leukocyte migration, T cell activation, and antigen-presentation might have further protected an improved β-cell function.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Obstetrics, Gynaecology and Reproductive Medicine (hsv//eng)

Nyckelord

Type 1 diabetes

Hashimoto´s thyroiditis

Graves´ disease

autoimmune Addison´s disease

antigen-presenting cells

B cells

non-classical monocytes

NK cells

memory CD8+ T cells

CDCP1

SLAMF1

inflammation

lymphocyte activation

pregnancy

β-cell function

C-peptide

plasma proteome

prolactin

prokineticin-1

glucagon

oral glucose tolerance test

mass cytometry

proximity extension assay

Medicinsk vetenskap

Medical Science

Klinisk immunologi

Clinical Immunology

Endocrinology and Diabetology

Endokrinologi och Diabetologi

Obstetrik och gynekologi

Obstetrics and Gynaecology

Publikations- och innehållstyp

vet (ämneskategori)

dok (ämneskategori)