Keywords:
Basal serum tryptase, mastocytosis, mast cells, Hereditary alpha tryptasemia
“To the Editor”
The level of Basal Serum Tryptase (BST) released by mast cells is still controversial because of the variability1,2in the constitutive secretion of α-tryptase. Indeed, an autosomalTPSAB1 gene replication has been associated with hereditary α-tryptasemia (HαT) present in more than 5% of the population worldwide34.
The main manufacturer of tryptase dosage has defined a 95th percentile reference level at 11.4 μg/L but numerous studies have reported lower levels of BST in the general population and a normal distribution. real life experience shows that most BST are much lower and some authors have adopted a reference value below 10 μg/L 5 or even below 8 μg/L 6.
This raises the epistemological question on the meaning of the ”reference range” which, according to ISO15189 rules, should be included in the result report provided for diagnosis. Reference range usually consider that values have a Gaussian distribution which is not the case here, in accordance with the genetic polymorphism.
In a preliminary study on 831 dosages for diagnosis (681 adults; mean age 56.0+16.7 years; 57.8% females), the serum BST median value was 4.97 [2.08; 9.48] µg/L (5th and 95th percentiles; FEIA ”ImmunoCAP tryptase” Phadia 250™; ThermoFisher Scientific, Uppsala, Sweden) and was independent of the patient age or gender but the distribution was not Gaussian (table 1). Interestingly, 6 (0.9%) out of the 681 adults had a tryptase below the limit of detection. In a prospective multicenter study gathering 636 dosages in healthy adult blood donors (HD) (49.3+ 17.9 years old, 45.6% females) from 7 laboratories using a Phadia 250™, median serum BST was 4.40 [2.03; 9.0] µg/L] and the distribution was not Gaussian. Seven (1.1%) BST were greater than 11.4 µg/L and 3 (0.47%) were undetectable (Table 1). Using a mathematical deconvolution analysis, we were able to identify a main population with a Gaussian distribution centered on a median value at 5.0 [3.0; 8.0] µg/L that could be considered as “low-producers”. A second population was observed with a median BST value at 10.0 [9.0; 11.0] µg/L(Figure 1a). Considering this new reference range, 50 (7.9%) of the HD are “high-producers” (BST>8 µg/L.
BST was not significantly different when performed on plasma (54 tests in adults, using a Phadia 250™) or in serum using a Unicap 100™ (27 adults). Global median BST tended to increase with age from 2.6 [1.2; 5.3] µg/L in 56 healthy 10-18 years old teenagers (mean age 15.8 ± 1.62, 46.4% female), significantly lower than in adults (p<0.001), up to 5.3 µg/L beyond 70 years of age. On the opposite, median BST was at 6.0 µg/L [2.5; 13.2 µg/L] in 51 healthy 3-day-old neonates, significantly higher than in adults (p<0.0014), Ten (19.6%) cases had BST greater than 8µg/L. Overall, a polynomial regression curve shows the nonlinear relationship of BST with age (Figure 1b) .