D2.24 - Vicilins – an overlooked group of storage protein allergens in walnut and hazelnut

Tree nuts contain three types of abundant storage proteins, 2S albumins, 7S globulins and 11S globulins. While all of these are known to act as food allergens, 2S albumins are the most well documented culprits in severe nut allergies. 7S globulins, also referred to as vicilins, have received less attention, perhaps because of their proteolytic processing into short fragments that may escape detection. This study aimed to assess the relative importance of walnut (WN) and hazelnut (HN) vicilins in comparison to other storage proteins available for IgE testing.

Leftover serum samples from children (median age 3.0 y) sensitized to WN (n=174) or HN (n=192) were collected in a major clinical laboratory in the US. Sera had been submitted by physicians for IgE testing to tree nuts but information on clinical history and observations underlying the requested testing was unavailable. IgE measurements were carried out using regular (rJug r 1 (2S), rCor a 14 (2S), nCor a 9 (11S)) or experimental (rJug r 2, rJug r 6, rCor a 11, rCor a 16 (all vicilins)) ImmunoCAP tests. IgE levels ≥0.35 kU_A/L were considered positive.

Among the WN positve samples, 77% were positive to rJug r 1, 69% to rJug r 2 and 56% to rJug r 6. Median IgE levels and IQRs among component positive samples were 11.9 (4.1-35.7) kU_A/L for rJug r 1, 8.5 (2.6-22.1) kU_A/L for rJug r 2 and 1.9 (0.7-4.0) kU_A/L for rJug r 6. Among the HN positve samples, 90% were positive to nCor a 9, 55% to rCor a 14, 38% to rCor a 11 and 67% to rCor a 16, with median IgE levels and IQRs of 5.8 (2.3-14.1) kU_A/L for nCor a 9, 2.5 (1.1-7.2) kU_A/L for rCor a 14, 1.2 (0.8-2.3) kU_A/L for rCor a 11 and 4.7 (1.7-12.0) kU_A/L for rCor a 16 among component positive samples. IgE levels to the two vicilins in each of the nuts showed only weak correlation, 0.196 for Jug r 2/Jug r 6 and 0.292 for Cor a 11/Cor a 16. In 44% of the WN positive samples, the combined levels of IgE to Jug r 2 and Jug r 6 exceeded 50% of the IgE level to the whole WN extract. A corresponding dominance of rCor a 11 and rCor a 16 occurred in 33% of the HN positive samples. Of 40 WN positive samples negative for rJug r 1, 25 (63%) tested positive for rJug r 2 and/or rJug r 6 and in the case of HN, 45/85 (53%) Cor a 14 negative samples tested positive for rCor a 11 and/or rCor a 16.

Our data suggest that vicilins play a major role in sensitization to WN and HN and may be important additions to diagnostic IgE testing.