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USMLE® Step 1 Question: Human Leukocyte Antigen Complex

Osmosis Team
Published on Jan 27, 2021. Updated on Feb 16, 2021.

Each week, Osmosis shares a USMLE® Step 1-style practice question to test your knowledge of medical topics. Today's case involves a young girl who is worried because of recent urinary issues and weight loss. These symptoms are upsetting her because she is trying to keep a certain weight for boxing lessons. Can you help her figure out what's happening by determining which gene is most likely present in her human leukocyte antigen complex?

A 12-year-old girl is brought to the clinic due to complaints of frequent, high-volume urination. For the past two months, the patient has been experiencing more frequent episodes of urination throughout the day, and the father says that the patient has been waking up at least three times a night to urinate. She has developed an unquenchable thirst and keeps a 2 liter water bottle next to her at all times. The patient is upset that she is losing weight despite eating more than normal in order to reach a certain size for boxing lessons. Her mother has a history of vitiligo. The patient’s temperature is 37.0°C (98.6°F), pulse is 100/min, respirations are 20/min, and blood pressure is 90/65 mmHg. Physical examination shows a tired-looking young female with dry mucous membranes and secondary sex characteristics consistent with Tanner stage II. Which of the following genes is most likely present in this patient’s human leukocyte antigen complex?


B. HLA-B27




 Scroll down to find the answer!

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The correct answer to today's USMLE® Step 1 Question is...


This patient likely has Type 1 Diabetes Mellitus (T1DM). Before we go into the full answer explanation, let's review the incorrect answers.

Incorrect answer explanations

The incorrect answers to today's USMLE® Step 1 Question are...


Incorrect: The HLA-A3 gene within the human leukocyte antigen complex is associated with increased susceptibility to multiple sclerosis, possibly by presenting myelin PLP1 self-peptide to autoreactive CD8-positive T cells.

B. HLA-B27

Incorrect: The HLA-B27 gene within the human leukocyte antigen complex is associated with increased susceptibility to ankylosing spondylitis, Behçet disease, juvenile idiopathic arthritis, psoriatic arthritis, rheumatoid arthritis, shingles, and Steven-Johnson syndrome/toxic epidermal necrolysis.


Incorrect: The HLA-DPB1 gene within the human leukocyte antigen complex is associated with increased susceptibility to granulomatosis with polyangiitis, juvenile idiopathic arthritis, and rheumatoid arthritis.


Incorrect: The HLA-DQB1 gene within the human leukocyte antigen complex is associated with increased susceptibility to narcolepsy with cataplexy. Most people with narcolepsy with cataplexy have a variant of the HLA-DQB1 gene.

Correct answer explanation

This patient is experiencing the classic symptoms associated with uncontrolled hyperglycemia, including polyuria, polydipsia, and weight loss with polyphagia. Along with her mother’s history of vitiligo, which suggests a possible inherited autoimmune-associated gene, this patient most likely has type 1 diabetes mellitus (T1DM).

In T1DM, the immune system targets and destroys the beta-cells of the pancreas. A common target is an enzyme inside beta cells called glutamic acid decarboxylase (GAD), which helps make gamma aminobutyric acid or GABA. GABA increases insulin release and also has a protective effect on the beta-cells. Without the protective effect of GABA, the number of beta cells progressively decreases, leading to the loss of endogenous insulin and the elevation of blood sugar levels.

The gene complex involved in the regulation of the immune response, and which is often associated with various autoimmune conditions, is called the human leukocyte antigen (HLA) system. These genes code for the major histocompatibility complex, or MHC, which is a protein that helps the immune system recognize foreign molecules and maintain self-tolerance. People with T1DM often have specific HLA haplotype genes in common: HLA-DR3 and HLA-DR4.

In T1DM, destruction of beta cells usually starts early in life, and individuals present with symptoms of diabetes before the age of 30. Their tissues are sensitive to insulin, but since there are fewer beta-cells, insulin levels are very low. 

In contrast, type 2 diabetes mellitus (T2DM) is defined by insulin resistance. Risk factors for T2DM include obesity, environmental factors, and a multitude of heritable genetic factors. Insulin levels are increased at the start, but as the islet cells tire out and die, the level drops. T2DM usually manifests after the age of 40 and presents similarly to type 1 diabetes with polyuria, polydipsia, polyphagia, and unintentional weight loss.

Major takeaways

Type 1 diabetes mellitus (T1DM) is an autoimmune condition that is associated with HLA-DR3 and HLA-DR4 genes. Destruction of pancreatic beta cells causes insulin levels to drop. Risk factors include a family history of autoimmune disorders. 


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The United States Medical Licensing Examination (USMLE®) is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). Osmosis is not affiliated with NBME nor FSMB.