Random Dermatology MCQ - HLA and Skin Disease

A 25-year-old man presents with well-demarcated, erythematous, silvery-scaled plaques on his elbows and knees. His father has a similar condition. Which of the following HLA alleles is most strongly associated with this disorder and plays a critical role in presenting cutaneous antigens to CD8+ T-cells, driving the inflammatory response?

A) HLA-C*06:02
B) HLA-B*27
C) HLA-DR4
D) HLA-B*51
E) HLA-A*29

Correct Answer: A) HLA-C*06:02

Explanation

This presentation is classic for psoriasis vulgaris, a common immune-mediated skin disorder with a strong genetic component.

Role of the Major Histocompatibility Complex (MHC) in Skin:

The MHC, known in humans as the Human Leukocyte Antigen (HLA) system, is a cluster of genes on chromosome 6 that encodes cell surface proteins essential for the immune system to recognize foreign molecules. There are two main classes:

1. MHC Class I (HLA-A, -B, -C): Expressed on nearly all nucleated cells, including keratinocytes. They present endogenously derived antigens (e.g., viral peptides, self-peptides) to CD8+ cytotoxic T-cells.

2. MHC Class II (HLA-DR, -DQ, -DP): Primarily expressed on professional antigen-presenting cells (e.g., Langerhans cells, dermal dendritic cells). They present exogenously derived antigens to CD4+ T-helper cells.

HLA Associations in Dermatology:

• Psoriasis Vulgaris: The strongest and most consistent genetic association is with HLA-C*06:02 (formerly part of the HLA-Cw6 serotype).

  • Mechanism: HLA-C*06:02 is an MHC Class I molecule. It is believed to present a self-peptide or a streptococcal cross-reactive peptide to CD8+ T-cells in the skin. This activation triggers the release of cytokines (e.g., IL-17, TNF-α) that lead to keratinocyte hyperproliferation and the characteristic plaques.

• Other Important HLA-Skin Disease Associations:

  • (B) HLA-B*27: Strongly associated with psoriatic arthritis, ankylosing spondylitis, and reactive arthritis.

  • (C) HLA-DR4: Associated with pemphigus vulgaris (an autoimmune blistering disease) and rheumatoid arthritis.

  • (D) HLA-B*51: The hallmark association for Behçet's disease.

  • (E) HLA-A*29: Associated with birdshot chorioretinopathy, an ocular condition, not a primary skin disorder.

Why HLA-C*06:02 is Key in Psoriasis:

The association with an MHC Class I allele explains the critical role of CD8+ T-cells in the pathogenesis of psoriasis. The autoinflammatory loop is thought to be initiated when these cytotoxic T-cells, activated by antigens presented by HLA-C*06:02, infiltrate the epidermis.

Note: Understanding HLA associations provides insight into disease pathogenesis, as the specific HLA allele often determines which antigens can be presented to T-cells, thereby initiating an autoimmune or inflammatory response. The HLA-C*06:02 association is a cornerstone in understanding the immunogenetics of psoriasis.