Can a Patient Have Celiac Disease with HLA-DQA105 but Not HLA-DQB102?
Yes, celiac disease can develop in patients carrying HLA-DQA105 without HLA-DQB102, though this represents a much lower genetic risk than carrying both alleles together. The critical question is whether the patient carries other celiac-associated alleles that can form disease-permissive HLA-DQ heterodimers.
Understanding HLA Heterodimer Formation in Celiac Disease
The AGA guidelines emphasize that clinicians must carefully evaluate all HLA alleles tested before determining a patient is HLA-negative for celiac disease, specifically looking for HLA DQ2.5 (DQA10501, DQB10201), HLA DQ8 (DQA103, DQB10302), HLA DQ2.2 (DQA10201, DQB10202), and HLA DQ7.5 (DQA105, DQB10301), as well as reviewing whether "half heterodimers" compatible with celiac disease are present 1.
The DQ2.5 Heterodimer: Cis vs. Trans Configuration
Most celiac patients (≥90%) carry the complete DQ2.5 heterodimer encoded by DQA105:01 and DQB102:01 genes 1.
These alleles can be inherited in two ways:
Patients with DQ2.5 in trans have similar celiac disease risk to those with a single copy of the cis haplotype, suggesting that forming the functional DQ2.5 heterodimer—regardless of configuration—is what matters for disease susceptibility 2.
Celiac Disease Risk with Isolated HLA-DQA1*05
Half-Heterodimer Scenarios
European collaborative data from 1,008 celiac patients identified 61 who carried neither complete DQ2 nor DQ8 heterodimers; 57 of these 61 patients (93%) encoded half of the DQ2 heterodimer—either DQA105 or DQB102 alone 3.
If your patient carries DQA105 without DQB102, celiac disease remains possible if:
The patient carries DQB1*0301 (forming HLA DQ7.5, encoded by DQA105 and DQB10301), which the AGA specifically lists as a celiac-compatible haplotype 1.
The patient carries DQB1*0202 (which could pair with DQA1*05 to form a variant DQ2 heterodimer, though this is less common) 1.
The patient carries other DQB1*02 variants not detected by the specific laboratory assay used (a critical pitfall—commercial laboratories may not report all celiac-associated alleles) 1.
Risk Stratification by Genotype
Research demonstrates a gene-dosage effect in celiac disease risk 4, 2:
- Highest risk: Homozygous for DQ2.5 (two copies of DQA105 and DQB102 in cis) 5.
- High risk: Heterozygous DQ2.5 in cis, or DQ2.5 in trans 5, 2.
- Moderate risk: DQ8 (DQA103 with DQB10302) 1.
- Lower risk: Single copy of DQB102 or DQA105 alone, or other non-standard combinations 5, 3.
The presence of a single DQA105 allele without DQB102 confers substantially lower risk than complete DQ2.5 or DQ8, but does not eliminate celiac disease possibility 5, 3.
Clinical Algorithm for This Patient
Step 1: Obtain Complete HLA Typing
- Request the laboratory provide all alleles tested, not just a "positive/negative" result for DQ2/DQ8 1.
- Specifically verify the presence or absence of:
Step 2: Interpret Based on Complete Genotype
If DQA105 is present with DQB10301: The patient carries HLA DQ7.5, which is celiac-compatible. Celiac disease cannot be ruled out 1.
If DQA105 is present with DQB10202: The patient may form a variant DQ2 heterodimer. Celiac disease cannot be ruled out 1.
If DQA105 is present with DQA103 and DQB1*0302: The patient carries DQ8. Celiac disease cannot be ruled out 1.
If DQA1*05 is present in complete isolation (no DQB1*02, *0202, *0301, or DQ8): The patient carries only a "half heterodimer." Celiac disease is extremely rare but not impossible—only 4 of 1,008 European celiac patients fell into this category 3.
Step 3: Clinical Context Matters
The AGA notes that "in the presence of a family history and a compatible HLA haplotype, mild enteropathy short of villus atrophy might be a form of celiac disease, even in the absence of serologies" 1.
If the patient has:
- Positive celiac serology (tTG-IgA, EMA) 1
- Duodenal biopsy showing villous atrophy 1
- First-degree relatives with celiac disease 1
- Associated autoimmune conditions (type 1 diabetes, autoimmune thyroid disease) 1
Then proceed with celiac disease diagnosis and management despite atypical HLA, as the negative predictive value of HLA testing is not 100% 1.
Critical Pitfalls to Avoid
Do not rely on incomplete HLA reports: Many commercial laboratories report only "DQ2-positive" or "DQ2-negative" without specifying which alleles are present. This can miss DQ7.5, DQ2.2, or trans configurations 1.
Do not assume HLA-DQA1*05 alone rules out celiac disease: While rare, celiac disease has been documented in patients with isolated half-heterodimers 3.
Do not use HLA testing as a primary diagnostic tool: HLA testing is most useful for its negative predictive value (>99% when both DQ2 and DQ8 are absent). A positive or partially positive result does not confirm celiac disease—it only indicates genetic susceptibility 1.
Ensure adequate gluten intake before testing: Patients must consume at least 10g of gluten daily for 6–8 weeks before serologic or histologic testing to avoid false-negative results 1.
Bottom Line
A patient with HLA-DQA105 but not HLA-DQB102 can develop celiac disease if they carry other celiac-permissive alleles (especially DQB1*0301 forming DQ7.5, or DQ8 alleles). The absence of DQB1*02 does not exclude celiac disease. Obtain complete HLA typing showing all alleles present, and interpret results in the context of serology, biopsy findings, family history, and clinical presentation. If all celiac-associated HLA alleles are truly absent (no DQ2.5, DQ2.2, DQ7.5, or DQ8), celiac disease is extremely unlikely but not impossible—fewer than 1% of celiac patients lack all known risk alleles 1, 3.