A survey of total IgE reference intervals reported by Scandinavian and British medical laboratories – a need for harmonisation

Figures & data

Figure 1. Data handling flowchart. ^a) Non-relevant laboratories were defined as accredited laboratories specialising in medical genetics, microbiology, toxicology, criminology, cyto-/histopathology or reproductive testing.

Figure 2. Adult total IgE reference intervals (only upper limits are shown) utilised in Scandinavia and the UK, compared to published upper reference limits (n=11 solid red points derived from 6 publications).

Table 1. Descriptives for acquired data sets, reference interval sources and adult total IgE upper reference limits reported by medical laboratories in Norway, Sweden, Denmark and the UK.

	Norway	Sweden	Denmark	UK
Total data sets acquired (response rate)	17 (100%)	16 (94%)	22 (85%)	67 (60%)
Source of reference interval
Package insert	11	14	5	13
Local or regional RI investigations	1	0	13	33
Recent publications	4	0	0	1
Unknown	1	2	4	20
Adult total IgE upper limit (kU/L)
Median	114	114	115	81
Range (min – max)	210(87 − 297)	44(85 − 129)	50(100 − 150)	248(2 − 250)

Figure 3. Paediatric total IgE reference interval upper limits, reported by medical laboratories (n = 122) in Scandinavia and the UK and those reported in the literature (solid red points, derived from six publications). The y-axis displays reported IgE upper reference limits on a logarithmic scale.

Table 2. Summary of adult total IgE reference interval studies published after 1990 utilising immunoassays, with the exception of Simoni et al. (2001) [13] utilising paper radio immunosorbent test (PRIST).

Subjects (location, number of participants)	Method	Subgroup	Adult upper reference limit (kU/L)			Reference
			95^th	97.5^th	99^th
Presumably healthy adults (from 10 Western European countries, N = 6 670)	ImmunoCAP	Non-smokers Males Females Smokers MalesFemales	169 148 220 194		341 300 446 392	Carosso et al. (2007) [8]
Presumably healthy adults (North Italy, N = 557: males n = 226, females = 331)	PRIST	Males Females		297 257		Simoni et al. (2001) [13]
Healthy adults accepted as volunteers for blood donation (Kuwait, N = 546)	Pharmacia CAP-Phadia	Mixed		602.5		Ezeamuzie et al. (1999) [47]
Presumably healthy adults (Tehran, Iran, N = 366)	ELISA	Mixed	250			Shoormasti et al. (2010) [12]
Healthy adults accepted as volunteers for blood donation (Norway, N = 252)	ImmunoCAP	Mixed	302	391		Vinnes et al. (2023) [17]
Presumably healthy adults (Salt Lake City area USA, N = 128: males n = 64, females n = 64)	ImmunoCAP	Mixed		214		Martins et al. (2014) [11]

Table 3. Summary of published paediatric total IgE reference interval studies performed using immunoassays identified by the literature review.

Subjects (location, number of participants)	Method	Subgroup	Paediatric upper reference limit (kU/L)		Reference
Salt Lake City area, USA, N = 1376 males N = 702, females N = 674	ImmunoCAP	Mixed	6 − 12 mo1 − 2 y3 y4 − 6 y7 − 8 y9 − 12 y13 − 15 y16 − 17 y	2.5 − 97.5^th 2 − 342 − 972 − 1992 − 3072 − 4032 − 6962 − 6292 − 537	Martins et al. (2014) [11]
Washington D.C. area, USA, N = 940 males N = 476, females N = 464	Abbott IMx	Males	0 − 12 mo1 − 3 y4 − 10 y11 − 15 y16 − 18 y	2.5 − 97.5^th 2 − 242 − 1494 − 2497 − 2805 − 268	S.J. Soldin et al. (1995) [16]
		Females	0 − 12 mo1 − 3 y4 − 10 y11 − 15 y16 − 18 y	0 − 205 − 558 − 2795 − 2957 − 698
Washington D.C. area, USA, N = 2691	Siemens Immulite 2000	Males	0 − <4 mo4 mo − <1 y1 − <3 y3 − <10 y10 − <13 y13 − <15 y15 − 18 y	2.5 − 97.5^th 1 − 401 − 1263 − 3984 − 9998 − 63110 − 56211 − 447	O.P. Soldin et al. (2008) [14]
		Females	0 − <4 mo4 mo − <1 y1 − <3 y3 − <10 y10 − <13 y13 − <15 y15 − 18 y	1 − 242 − 633 − 1413 − 3989 − 40723 − 3555 − 355
Greater Toronto area, Canada	Abbott Architect ci4100 (N = 699)Beckman Coulter Immunoassay Systems (N = 600)	Mixed	0 − <7 y 7 − 19 y	2.5 − 97.5^th <25 − 440 <25 − 450	CALIPERKelly et al. (2015) [10] Karbasy et al. (2016) [9]
		Mixed	0 − <2 y 2 − <8 y 8 − <19 y	0 − 809 2 − 786 3 − 833
Korea. Randomly selected nationwide elementary and middle schools, N = 3679	ImmunoCAP	Mixed	6 − 7 y	95^th <877	Kim et al. (2017) [15]
			12 − 13 y	<716

Table 4. Reference intervals provided in the package insert by market leaders of total IgE analysis in Europe with information on the international reference preparation (IRP), type of upper limit and source of data.

			Suggested RIs by package insert (kU/L)
Manufacturer	Assay / Platform	Traceability as stated by package insert	Adult	Paediatric	Percentile	Source of adult RIs	Source of paediatric RIs
Thermo Fisher	ImmunoCAP [18]	2nd WHO (75/502) IRP, or the 3rd WHO (11/234) IRP	<114	0 − 6 w <2.36 w − 3 mo <4.13 − 6 mo <7.36 mo − 1 y <131 − 2 y <232 − 3 y <323 − 4 y <404 − 5 y <485 − 6 y <566 − 8 year <718 − 10 year <85	Geometric mean + 1 SD	Zetterstrøm et al. (1981) [27]	Bhalla et al. (1982) [29] Kjellman et al. (1976) [26]
Roche Diagnostics	Cobas [24]	2nd WHO (75/502) IRP	<100	<1 y <151 − 5 y <60 6 − 9 y <9010 − 15 y <200	Not specified	Dati et al. (1982) [28]	Dati et al. (1982) [28]
Abbott	ARCHITECT c [25]	2nd WHO (75/502) IRP	<100	<1 y <151 − 5 y <60 6 − 9 y <9010 − 15 y <200	Not specified	Dati et al. (1982) [28]	Dati et al. (1982) [28]
Siemens Healthineers	Advia Centaur [20]	2nd WHO (75/502) IRP	<158	<1 y <117.41 − 4 y <313.55 − 10 y <555.111 − 15 y <481.1	Adult: 95^th percentile Paediatric: Geometric mean + 2SD	Internal non-published study (n = 103 adults)	Internal non-published study (n = 109 children)
	Immunlite 2000 [19]	2nd WHO (75/502) IRP	<87	0 − 1 y <291 − 2 y <492 − 3 y <453 − 9 year <52	95^th percentile	Not specified	Not specified
	Attelica [21]	2nd WHO (75/502) IRP	<158	<1 y <117.41 − 4 y <313.55 − 10 y <555.111 − 15 y <481.1	Adult: 95^th percentile Paediatric: Geometric mean + 2SD	Internal non-published study (n = 103 adults)	Internal non-published study (n = 109 children)
	BN II Nephelometer [22]	WHO-standardized determination of IgE (unspecified)	<100	Neonates <1.5 < 1 y <151 − 5 y <606 − 9 y <90	Not specified	Dati et al. (1982) [28]	Dati et al. (1982) [28]
Beckman Coulter	IMMAGE Immuno chemistry systems [23]	2nd WHO (75/502) IRP	<165	Not provided	Adult: 95^th percentile	Internal non-published study (n = 134 non-allergic adults)	--

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