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\begin{document}

\title{Basal serum tryptase: a critical reconsideration of reference values}



\author[1]{Claude LAMBERT}%
\author[1]{Fabien FRANCOIS}%
\author[2]{Brigitte LE MAUFF}%
\author[1]{Louis WAECKEL}%
\author[3]{Luc de Chaisemartin}%
\author[4]{Thierry Tabary}%
\author[5]{Erwan Dumontet}%
\author[6]{Jean-Claude Lecron}%
\author[7]{Benoit DELAMARE}%
\author[8]{Ahmed BOUMEDIENE}%
\author[9]{Angélique Grenier}%
\author[10]{Rémi Pescarmona}%
\author[10]{Lorna GARNIER}%
\affil[1]{Centre Hospitalier Universitaire de Saint-Etienne Laboratoire d'Immunologie Biologique}%
\affil[2]{Centre Hospitalier Universitaire de Caen Laboratoire de Biologie Medicale}%
\affil[3]{Hopital Bichat - Claude-Bernard}%
\affil[4]{Centre Hospitalier Universitaire de Reims Pole Biologie}%
\affil[5]{Centre Hospitalier Universitaire de Rennes}%
\affil[6]{Centre Hospitalier Universitaire de Poitiers}%
\affil[7]{Laboratoire Biochimie CHR Orléans}%
\affil[8]{Centre Hospitalier Universitaire de Limoges}%
\affil[9]{Service de Biologie Médicale CH Aulnay-sous-Bois}%
\affil[10]{Centre Hospitalier Lyon-Sud Centre de Biologie et de Pathologie Sud}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\textbf{Basal serum tryptase:}

\textbf{a critical reconsideration of reference values}

Fabien FRANCOIS\textsuperscript{1}, Brigitte LE
MAUFF\textsuperscript{2,} Louis WAECKEL\textsuperscript{1}, Luc de
CHAISEMARTIN\textsuperscript{3}, Thierry TABARY\textsuperscript{4},
Erwan DUMONTET\textsuperscript{5}, Jean Claude
LECRON\textsuperscript{6}, Benoit DELAMARE \textsuperscript{7}, Ahmed
BOUMEDIENE \textsuperscript{8}, Ang\selectlanguage{ngerman}élique
CHAUVINEAU-GRENIER\textsuperscript{9}, Remi
PESCARMONA\textsuperscript{10}, Lorna GARNIER\textsuperscript{10},
Claude LAMBERT\textsuperscript{1} and French network of Hospital
biologist in Allergology (AllergoBioNet).

\textsuperscript{1}Laboratoire d'immunologie clinique, Hôpital Nord,
Saint-Étienne, France

\textsuperscript{2}Laboratoire Immunologie CHU Caen

\textsuperscript{3}APHP, Laboratoire d'Immunologie, Hôpital Bichat,
Paris, France

\textsuperscript{4}Laboratoire d'Immunologie CHU Reims, Pôle de Biologie
Territoriale, Reims,

\textsuperscript{5}Laboratoire Immunologie CHU Rennes

\textsuperscript{6}Laboratoire Immunologie CHU Poitiers

\textsuperscript{7}Laboratoire Biochimie CHR Orléans

\textsuperscript{8}Laboratoire Immunologie CHU Limoges

\textsuperscript{9}Service de Biologie Médicale CH Aulnay-sous-Bois

\textsuperscript{10}Laboratoire Immunologie CH Lyon sud

\textbf{Corresponding author:}

Claude LAMBERT (claude.lambert@chu-st-etienne.fr)

Laboratoire d'Immunologie clinique, pôle de Biologie, Hôpital Nord, CHU
Saint-Étienne

42055 Saint-Etienne Cedex 2 FRANCE

Tel: +33 477120513; Fax: +33 477120552

Research supported by Immunology laboratory / University
Hospital~Saint-Etienne, FRANCE,

\textbf{Abbreviations:}

\textbf{BST}: Basal Serum Tryptase\textbf{FEIA:} Fluorimetric
Enzyme-Linked Immunoassay\selectlanguage{greek}\textbf{HαT:}\selectlanguage{english} Hereditary \selectlanguage{greek}α
\selectlanguage{english}tryptasemia\textbf{HD}: healthy donors

\textbf{Acknowledgment:}

\textbf{Running title:} Basal serum tryptase: a critical reconsideration
of reference values

Author contribution

Fabien FRANCOIS\textsuperscript{1}, Brigitte LE
MAUFF\textsuperscript{2,} Luc de CHAISEMARTIN\textsuperscript{3},
Thierry TABARY\textsuperscript{4}, Erwan DUMONTET\textsuperscript{5},
Jean Claude LECRON \textsuperscript{6}, Benoit DELAMARE
\textsuperscript{7}, Ahmed BOUMEDIENE \textsuperscript{8}, Ang\selectlanguage{ngerman}élique
CHAUVINEAU-GRENIER\textsuperscript{9}, Remi
PESCARMONA\textsuperscript{10}, Lorna GARNIER\textsuperscript{10},
Claude LAMBERT\textsuperscript{1}

Have contributed in getting the healthy donor data as well as technical
conditions

Fabien FRANCOIS\textsuperscript{1} did the data collection and
statistical analysis, bibliography and part of writing

Louis WAECKEL\textsuperscript{1,} Claude LAMBERT\textsuperscript{1},
initiated the study, supervised the data collection, data analysis and
paper writing

Brigitte LE MAUFF \textsuperscript{2,} Luc de
CHAISEMARTIN\textsuperscript{3}, Thierry TABARY\textsuperscript{4},
Erwan DUMONTET\textsuperscript{5} actively participated in paper writing

\textbf{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 variability\textsuperscript{1,2}in the
constitutive secretion of \selectlanguage{greek}α-\selectlanguage{english}tryptase. Indeed, an autosomal\emph{TPSAB1}
gene replication has been associated with hereditary \selectlanguage{greek}α-\selectlanguage{english}tryptasemia (H\selectlanguage{greek}α\selectlanguage{english}T)
present in more than 5\% of the population
worldwide\textsuperscript{34}.

The main manufacturer of tryptase dosage has defined a
95\textsuperscript{th} percentile reference level at 11.4 \selectlanguage{greek}μ\selectlanguage{english}g/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 \selectlanguage{greek}μ\selectlanguage{english}g/L \textsuperscript{5} or even below 8 \selectlanguage{greek}μ\selectlanguage{english}g/L
\textsuperscript{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{]} \selectlanguage{greek}µ\selectlanguage{english}g/L (5\textsuperscript{th} and
95\textsuperscript{th} 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\emph{+} 17.9 years old,
45.6\% females) from 7 laboratories using a Phadia 250, median serum
BST was 4.40 {[}2.03; 9.0{]} \selectlanguage{greek}µ\selectlanguage{english}g/L{]} and the distribution was not
Gaussian. Seven (1.1\%) BST were greater than 11.4 \selectlanguage{greek}µ\selectlanguage{english}g/L and 3 (0.47\%)
were undetectable \textbf{(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{]} \selectlanguage{greek}µ\selectlanguage{english}g/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{]}
\selectlanguage{greek}µ\selectlanguage{english}g/L\textbf{(Figure 1a).} Considering this new reference range, 50
(7.9\%) of the HD are ``high-producers'' (BST\textgreater{}8 \selectlanguage{greek}µ\selectlanguage{english}g/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{]} \selectlanguage{greek}µ\selectlanguage{english}g/L in 56 healthy 10-18 years old teenagers (mean age 15.8 \selectlanguage{ngerman}±
1.62, 46.4\% female), significantly lower than in adults
(p\textless{}0.001), up to 5.3 \selectlanguage{greek}µ\selectlanguage{english}g/L beyond 70 years of age. On the
opposite, median BST was at 6.0 \selectlanguage{greek}µ\selectlanguage{english}g/L {[}2.5; 13.2 \selectlanguage{greek}µ\selectlanguage{english}g/L{]} in 51 healthy
3-day-old neonates, significantly higher than in adults
(p\textless{}0.0014), Ten (19.6\%) cases had BST greater than 8\selectlanguage{greek}µ\selectlanguage{english}g/L.
Overall, a polynomial regression curve shows the nonlinear relationship
of BST with age \textbf{(Figure 1b)} .

\textbf{Conclusion}

We found that the non-Gaussian distribution of BST in healthy population
could be explained by a two population model in agreement with a
previous work\textsuperscript{5,6}. A great majority has a median BST at
5.0 \selectlanguage{greek}µ\selectlanguage{english}g/L and a 95\textsuperscript{th} percentile at 8 \selectlanguage{greek}µ\selectlanguage{english}g/L. We thus
propose to adopt a new threshold at 8\selectlanguage{greek}µ\selectlanguage{english}g/L and to suspect BST above 8\selectlanguage{greek}µ\selectlanguage{english}g/L
as being part of the minority of healthy people with gene duplication
and potentially H\selectlanguage{greek}α\selectlanguage{english}T, to be confirmed by genetic analysis according to
the eventual symptoms. This threshold is lower in teenagers (5.5 \selectlanguage{greek}µ\selectlanguage{english}g/L)
and slightly higher above the age of 70 (8.5 \selectlanguage{greek}µ\selectlanguage{english}g/L). In addition, we
describe that a small minority of HD have an apparent defect in basal
tryptase production that needs to be explored genetically.



\textbf{Table 1}\selectlanguage{english}
\begin{longtable}[]{@{}llllllllllll@{}}
\toprule
\begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
Laboratories\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
\textbf{nb}\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
\textbf{Sample type}\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
\textbf{instrument}\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
\textbf{Age mean-SD} \textbf{(range)}\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
\textbf{BST} \textbf{Med} \textbf{{[}5-95 \%{]}}\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
\textbf{F} \textbf{Med} \textbf{{[}5-95 \%{]}}\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
\textbf{M} \textbf{Med} \textbf{\% of M} \textbf{{[}5-95 \%{]}}\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
\selectlanguage{greek}\textbf{\textless{}1µg/L}\selectlanguage{english} \textbf{Nb (\%)}\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
\selectlanguage{greek}\textbf{\textgreater{}8 µg/L}\selectlanguage{english} \textbf{Nb (\%)}\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
\selectlanguage{greek}\textbf{\textgreater{}11.4 µg/L}\selectlanguage{english} \textbf{Nb (\%)}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
local\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
routine\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
diagnosis\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
adults\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
681 (82.5\%)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
serum\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
adults\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
U250\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
56.0 \selectlanguage{ngerman}± 16.7 (20-94)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
4.97 {[}2.08; 17.4{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{(57.8\%)} 4.79 {[}2.1; 16.6{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{(42.2\%)} 5.47 {[}2.2; 17.7{]} NS\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
6 (0.9\%)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
147 (21.6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
76 (11.2\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
children teenagers\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
143 (17.3\%)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
serum\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
children teenagers\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
U250\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
10.4 \selectlanguage{ngerman}± 6.2 (0-20)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
4.71 {[}2.14; 18.1{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{(42.7\%)} 4.21 {[}2.1; 11.5{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{(57.3\%)} 5.06 {[}2.2; 19.1{]} NS\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
26 (18.2\%)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
16 (11.2\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
Interlab\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
healthy\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
donors\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
(HD)\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
7 labs\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
636\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
serum\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
adults\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
U250\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
49.3 \selectlanguage{ngerman}± 17.9 (18-95)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
4.4 {[}2.0; 9.0{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
(56.5\%) 4.6 {[}2.2; 8.8{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
(43.5\%) 4.7 {[}2.0; 9.1{]} NS\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
3 (0.47\%)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
50 (7.9\%)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
7(1.1\%) {[}12.5-20.3{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
1 lab\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
54\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Plasma\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
adults\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
U250\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
NA\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
4.0 {[}1.7; 10.2{]} NS\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
NA\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
NA\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
6 (11.1\%)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
2 (3.7\%) {[}14.9-20.0{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
1 lab\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
27\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
serum\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
adults\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
U100\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
55.5 \selectlanguage{ngerman}± 24.4 (18-95)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
3.4 {[}1.9; 7.3{]} NS\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
(48.1\%) 4.0 {[}2.0; 7.0{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
(51.9\%) 3.4 {[}18; 10.8{]} NS\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
1 (3.7\%)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
1 (3.7\%) {[}17.6{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
3 labs\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
56\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
serum\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
teenagers\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
U100 (6) U250 (50)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
15.8 \selectlanguage{ngerman}± 1.62 (10-117.9)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
2.6 {[}1.2-5.3{]} \emph{p\textless{}0.001}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
(46.4\%) 2.7 {[}1.2; 5.3{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
{[}53.6\%) 2.6 {[}1.3; 5.1{]} NS\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
1 (1.8\%) {[}8.3{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
1 lab\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
15\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
serum\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
children\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
U100\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
3.9 \selectlanguage{ngerman}± 2.55 (1-9)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
5.0 {[}3.2; 11.1{]} \emph{p=0.0184}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
(20\%) 5.0 {[}4.3-7.5{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
(80\%) 5.0 {[}3.2; -11.5{]} \emph{NS}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
3 (20\%)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
1(6.7\%) {[}13,0{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
1 lab\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
51\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
serum\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
new borns\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
U250\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
3days\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
6.0 {[}2.5;13.2{]} \emph{p\textless{}0.0001}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
(56.9\%) 5.3 {[}2.6-9.0){]} NS\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
(43.1\%) 6.1 {[}4.2; 11.1{]} p=0.034\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
10 (19.6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
2 (3.9\%){[}11.6-13.2{]}\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 1.} Basal Serum tryptase (BST) from different
laboratories. First 2 rows: routine diagnosis BST median values in 681
adults and 143 children in a single laboratory. Last 6 rows BST median
values performed to determine local reference value in heathy donors, in
adults, dosage performed either on serum or plasma, in two different
type of instruments, and in different age in children from 3 days old
newborns, in 1-9 years old children and 10-18 years old. Number of
patients above the classical threshold (11.4\selectlanguage{greek}µ\selectlanguage{english}g/L) or the proposed
threshold (8\selectlanguage{greek}µ\selectlanguage{english}g/L). Tryptase dosage was below the limit of detection of
the technique (1\selectlanguage{greek}µ\selectlanguage{english}g/L) in few people. Data show mean (+1 SD) or median
and {[}5-95 \%{]} range. Female and male results show (\%) of the
population before median and range. BST values according to the age are
compared to the adult, Unicap 250 values while female BST values



\textbf{Figures}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\selectlanguage{greek}\textbf{Figure 1. BST levels below 11.4 µg/L suggest two different
subpopulations and reference values as a function of age, and.}\selectlanguage{english}A ,
Mathematical density curves for healthy donors suggesting 2 different
subgroups with a normal distribution by tryptase ranges, a reference
population assumed to have no TPSAB1 duplication and one of which had
almost double BST values (n=655). Medians and percentiles
(5\textsuperscript{th} and 95\textsuperscript{th}) of each are also
shown. B , Polynomial curve (red dashed line) representing the evolution
of BST as a function of age calculated with medians (red dots) for
healthy donors by age categories. The grey area on either side
represents a 95\% confidence interval. The median tryptase value of all
healthy donors for whom age was available is also shown (black dashed
line). Values with no associated age have been excluded (n=533).

1. Waters AM, Park HJ, Weskamp AL, et al. Elevated Basal Serum Tryptase:
Disease Distribution and Variability in a Regional Health System.
\emph{The journal of allergy and clinical immunology In practice.} 2022.

2. Aniceto V, Dias MM, Melo JML, et al. Serum Baseline Tryptase Level as
a Marker for the Severity of Anaphylaxis. \emph{International archives
of allergy and immunology.}2019;179(3):201-208.

3. Lyons JJ. Hereditary Alpha Tryptasemia: Genotyping and Associated
Clinical Features.\emph{Immunology and allergy clinics of North
America.}2018;38(3):483-495.

4. Khoury P, Lyons JJ. Mast cell activation in the context of elevated
basal serum tryptase: genetics and presentations. \emph{Current allergy
and asthma reports.}2019;19(12):55.

5. Komarow HD, Hu Z, Brittain E, Uzzaman A, Gaskins D, Metcalfe DD.
Serum tryptase levels in atopic and nonatopic children. \emph{The
Journal of allergy and clinical immunology.} 2009;124(4):845-848.

6. Luskin KT, White AA, Lyons JJ. The Genetic Basis and Clinical Impact
of Hereditary Alpha-Tryptasemia.\emph{The journal of allergy and
clinical immunology In practice.}2021;9(6):2235-2242.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Tryptasemia-figure/Tryptasemia-figure}

\end{center}
\end{figure}

\textbf{Hosted file}

\verb`Letter tryptas\selectlanguage{ngerman}émie 2022 12 20_LAMBERT_Table 1.docx`  available at \url{https://authorea.com/users/570277/articles/615985-basal-serum-tryptase-a-critical-reconsideration-of-reference-values}

\selectlanguage{english}
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\end{document}

