Hereditary angioedema (HAE) is a rare but potentially life-threatening genetic disorder causing recurrent episodes of severe swelling of the skin and mucosa.¹ It results from either a deficiency (type 1) or dysfunction (type II) of C1 esterase inhibitor (C1-INH).^1,2 Diagnosis traditionally relies on laboratory assays measuring C1-INH levels, function, and complement component 4 (C4) levels.² However, the Asia Pacific Association of Allergy, Asthma, and Clinical Immunology (APAAACI) Survey revealed regional disparities in access to C1-INH function testing and SERPING1 genotyping.¹ Given these limitations, dried blood spot (DBS) testing is emerging as a promising alternative for diagnosis and family screening.³ At the AAAAI/WAO Joint Congress 2025, Dr. Jane Wong, from the University of Hong Kong presented key findings on the potential of DBS testing in facilitating HAE screening.³      

This study was conducted to validate DBS results against conventional laboratory assays in patients with confirmed C1-INH HAE and assess its potential for broader use within the Screening Programme Providing Outreach for Testing Hereditary Angioedema (SPPOT-HAE).³ The study was divided into two parts.³ Part I involved 16 Chinese patients with C1-INH HAE from seven families, who participated in a validation study to assess DBS for its ability to detect C4, C1-INH, and functional C1-INH (fC1-INH).³ The results obtained from DBS were then compared with those from standard laboratory assays to determine their reliability and diagnostic accuracy.³ Part II explored the use of DBS for family screening within a large Chinese family, where several relatives had previously declined conventional blood testing.³

The study found a strong correlation between DBS and conventional assays in measuring C4 (r=0.957, p<0.0001), C1-INH (r=0.946, p<0.0001), and fC1-INH levels (r=0.981, p<0.0001), with no false-negative results detected for C4 (9/9), C1-INH (9/9), and fC1-INH (3/3).^3,4 These results indicate that DBS is a reliable tool for HAE screening.³ Given its diagnostic accuracy, DBS testing also offers several advantages over conventional laboratory methods, including simpler blood collection, greater sample stability, and easier transport.^3,4 Furthermore, DBS testing has proven to be an effective approach in family screening, as demonstrated by the SPPOT-HAE outreach program, which successfully recruited nine additional relatives in one large Chinese HAE family for screening, of whom two (22%) were confirmed to have HAE.³ The positive outcomes of the program also highlighted DBS’s potential to overcome prior barriers to family screening, such as logistical challenges and reluctance to visit medical facilities.⁴                                  

In conclusion, the success of DBS in this study highlights its potential for wider adoption in HAE screening, especially among resource-constrained regions.⁴ While the current study focused on measuring C4, C1-INH, and fC1-INH, the utility of DBS may extend beyond these biomarkers.³ However, before DBS can be widely implemented in clinical practice, larger-scale validation studies are needed.³ Future research should include healthy control populations to confirm the accuracy and reliability of DBS across different demographics.³