Involvement of heat shock proteins in gluten-sensitive enteropathy

Table 1 Classification of heat shock proteins[46,113]

Family	Subunit MW (kDa)	Family members	Cellular localization
HSP100	80-110	HSP100, HSP104	Cytoplasm, nucleus, mitochondria, plasma membrane
HSP90	82-96	HSP90α, HSP90β	Cytoplasm, nucleus, mitochondria, endoplasmic reticulum
HSP70	67-76	HSP70, HSP72, HSP73, HSP80	Cytoplasm, nucleus, mitochondria, endoplasmic reticulum, lysosomes, extracellular compartments
HSP60	58-65	HSP60, HSP65	Mitochondria
Small HSPs	8-40	αB-crystallin, HSP25, HSP27, ubiquitin	Cytoplasm, nucleus
Others (not ubiquitous)	Various	HSP33	Various

MW: Molecular weight; HSP: Heat shock protein.

Table 2 Involvement of heat shock proteins in coeliac disease

Samples	Investigation	Localization/major findings	Ref.
Duodenal biopsies from 16 children with newly diagnosed CD, 9 maintained on GFD, 10 controls	HSP72 mRNA expression, protein level and localization	HSP72 mRNA and protein are increased in CD, and decreased by GFD. HSP72 was localized in villous enterocytes of the epithelium and lamina propria immune cells	[102]
Duodenal biopsy specimens from 30 HLA-DQ2 (+) NCGS and 15 CD patients maintained on GFD	HSP27 or HSP70 mRNA expression, before and after challenge with gluten-containing bread daily for 3 d	mRNA expression of HSP27 and HSP70 in the duodenal mucosa was not different in any of the groups	[103]
Jejunal biopsies from 78 children with clinical suspicion of CD	Epithelial HSP65 expression	Increased mitochondrial HSP65 expression in the jejunal mucosa in 80% (16/20) of children with CD and in 24% (14/58) of non-CD patients. Strong correlation between HSP65, γδ + T-cells and serum IgA endomysial autoantibodies. HSP65 is a potential mucosal integrity modulator	[104]
Duodenal biopsies from 12 patients with CD and 10 controls	Small HSP αB-crystallin expression and distribution	Increased αB-crystallin in CD, localized in the supra-nuclear region of enterocytes in the duodenal mucosa	[105]
Blood samples from 128 patients with CD and 94 healthy individuals	HSPA1A gene (HSP70-1) polymorphism	Altered frequency of an intermediate HSPA1A allele in CD (64.5%) vs normal (37.2%). HSP70-1 gene is part of a high-risk haplotype for CD	[106]
Blood samples from 19 families with CD patients and 95 healthy individuals	HLA-linked HSPA1B gene (HSP70-2) polymorphism	Altered HSPA1B allele frequencies in CD vs normal and non-affected MHC haplotypes	[107]

CD: Coeliac disease; GFD: Gluten-free diet; HSP: Heat shock protein; NCGS: Non-coeliac gluten sensitivity; Ig: Immunoglobulin; HLA: Human leukocyte antigen; MHC: Major histocompatibility complex.