MRCP UK EXAMINATIONS

CLINICAL ENCOUNTERS

ANKYLOSING SPONDYLITIS

Question [CLICK ON ANY CHOICE TO KNOW THE RIGHT ANSWER]
Formation of HLA-B27 homodimers due to misfolding in the endoplasmic reticulum Accumulation of misfolded proteins in cells causes a proinflammatory intracellular stress response Expression of HLA-B27 homodimers recognized as foreign antigens What is the pathogenesis theory
A
Arthritogenic peptides
B
Self-association of the HLA-B27 molecule
C
Alteration of intracellular handling of microbes due to HLA-B27
D
None of the above
Explanation: 

Detailed explanation-1: -(3) HLA-B27 Misfolding: The formation of misfolded oligomers and BiP binding by newly synthesized HLA-B27 heavy chains causes ER stress, which has intrinsic effects on cellular function that are hypothesized to promote development of spondyloarthritis.

Detailed explanation-2: -HLA-B27 binds and presents peptides from influenza, HIV, Epstein-Barr virus, and other viruses. This leads to vigorous and specific cytotoxic T lymphocyte responses, which play an important role in the body’s immune response to these viruses.

Detailed explanation-3: -HLA-B27 misfolding is related to UPR (Unfolded Protein Response) and EOR (ER Overload Mechanism), since UPR mechanism protect ER homeostasis against misfolded protein and EOR system provide normal ER function to work on accumulating protein.

Detailed explanation-4: -The protein is called human leukocyte antigen B27 (HLA-B27). Human leukocyte antigens (HLAs) are proteins that help the body’s immune system tell the difference between its own cells and foreign, harmful substances. They are made from instructions by inherited genes.

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