Regarding the immune system, which of the following statements are correct: a) IgG4‑related disease exclusively affects the gastrointestinal tract; b) Patients who have undergone splenectomy are more susceptible to Haemophilus influenzae infection; c) Heterozygous carriers of the cystic fibrosis transmembrane conductance regulator (CFTR) gene are protected from Brucella because it uses this receptor to enter the body; d) Rh (Rhesus) system antigens are not expressed on endothelial cells and therefore do not affect transplantation outcomes; e) Determination of human leukocyte antigen (HLA) antigens is a decisive test for matching donor and recipient in transplantation?

Immune System Question: Correct Statement Analysis

Statement (e) is correct: HLA antigen determination is a decisive test for determining donor-recipient pairs in transplantation. 1

Analysis of Each Statement

Statement A: IgG4-Related Disease and Gastrointestinal System

This statement is FALSE. IgG4-related disease (IgG4-RD) is a multi-organ immune-mediated fibroinflammatory disorder that can affect virtually all organs, not exclusively the gastrointestinal system 2. The disease encompasses multiple previously isolated conditions including:

• Type 1 autoimmune pancreatitis
• Mikulicz's disease (salivary and lacrimal glands)
• IgG4-related kidney disease
• IgG4-related sialadenitis 3, 4

The condition is characterized by lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis across multiple organ systems 2.

Statement B: Splenectomy and Haemophilus influenzae

This statement is FALSE. While post-splenectomy patients are indeed at increased risk for encapsulated bacterial infections, the primary organisms of concern are:

• Streptococcus pneumoniae (most common)
• Neisseria meningitidis
• Haemophilus influenzae (but this is NOT the primary concern)

The statement incorrectly emphasizes H. influenzae as the main pathogen. Splenectomy in transplant recipients has been largely abandoned due to unclear efficacy and potentially serious adverse effects including death and infectious complications 1.

Statement C: CFTR Carriers and Brucella Protection

This statement is FALSE. There is no established evidence that heterozygous carriers of the CFTR gene (cystic fibrosis transmembrane conductance regulator) are protected from Brucella infection. While elevated IgG4 levels have been documented in cystic fibrosis patients 5, this does not indicate that CFTR serves as a receptor for Brucella entry or that carriers have protection against this pathogen.

Statement D: Rhesus Antigens and Transplantation

This statement is FALSE. While Rh antigens are primarily expressed on red blood cells, the statement's implication that they "do not affect transplantation outcomes" is misleading. The critical antigens for solid organ transplantation are HLA antigens, not Rh antigens. However, ABO blood group compatibility (which includes consideration of red cell antigens) remains essential for transplantation 1.

Statement E: HLA Antigen Determination in Transplantation

This statement is CORRECT. HLA antigen determination is indeed decisive for donor-recipient matching in transplantation 1. The evidence supporting this includes:

High-Resolution HLA Typing Requirements

• High-resolution HLA genotyping (2-field resolution) is recommended with Grade 1A evidence for kidney transplantation to ensure correct assessment of anti-HLA antibody specificity to donors 1
• HLA-A, -B, -C, and -DRB1 high-resolution testing should be performed on all potentially matched donors 1
• DQB1 typing is increasingly recognized as critical, with HLA-DQ mismatches significantly increasing graft loss risk (HR 1.12) 1, 6

Clinical Impact of HLA Matching

• Each HLA mismatch at HLA-A, -B, -C, and -DRB1 can reduce survival by 5-10% depending on disease risk status 6
• Over 50% of long-term kidney graft failure is attributed to donor-specific antibody (DSA)-mediated rejection 1, 6
• 54-77% of patients with de novo DSA develop antibodies against HLA-DQ, associated with antibody-mediated rejection and graft loss 6

Organ-Specific Recommendations

The American Journal of Transplantation provides graded recommendations for HLA typing across organ types 1:

• Kidney: Grade 1A for high-resolution HLA genotyping
• Heart: Grade 1B for high-resolution HLA genotyping
• Lung: Grade 1B for high-resolution HLA genotyping
• Liver: Grade 2C for high-resolution HLA genotyping

Technical Considerations

• Both HLA-DQA1 and HLA-DQB1 chains must be assessed as heterodimers, as both contribute to immunogenicity 1, 7
• Luminex-based typing provides sufficient resolution to eliminate most common ambiguities for solid organ typing purposes 1, 8
• Allele-level resolution is superior to antigen-level typing for accurate compatibility assessment 1, 7

Common Pitfalls to Avoid

• Do not rely on antigen-level matching alone when allele-level differences exist (e.g., B44:02 vs. B44:03) 7
• Do not neglect HLA-DQ matching, which has historically been underemphasized but is critical for long-term outcomes 1, 6
• Do not ignore both chains of HLA-DQ (DQA1 and DQB1) when assessing compatibility 1, 7
• Do not assume elevated IgG4 levels are specific to IgG4-RD without excluding other conditions including infections, autoimmune diseases, and malignancies 5