Colorectal mucosal histamine release by mucosa oxygenation in comparison with other established clinical tests in patients with gastrointestinally mediated allergy

Table 1 Patient data, allergens used for oral provocation, colorectal mucosal histamine release, skin prick test, serum IgE detection (RAST test), and patient’s history

Pat.No.	Sex	Age	Allergen	Oral	Colorectal	Skin	RAST	H
				provocation	HR	test	IgE
1WT	F	44	Cheese	+	+	-	+	?
			Rye bran	-	-	+	+	?
2DF	F	49	House dust	+	+	+	+	?
			Rye pollen	-	+	-	+	?
3OL	M	41	Soya flour	+	+	+	+	+
			Rye flour	-	-	-	+	?
4CG	M	23	Rye flour	+	+	-	-	-
5NA	F	42	Wheat flour	+	-	+	+	?
			Soya flour	-	-	-	+	?
6IL	F	43	Wheat bran	+	+	-	+	?
			Barley flour	-	-	+	-	?
7GG	F	19	Soya flour	+	+	+	+	?
			Wheat flour	-	+	-	+	?
8FJ	F	25	Soya lecithin	+	-	+	+	+
			Milk	-	-	-	+	+
9MR	F		Milk	+	-	-	-	-
			Potato	-	-	-	-	-
10MB	F	23	Wheat/rye	+	-	+	+	-
			Egg	-	-	-	-	+
11FB	F	51	Wheat flour	+	+	-	+	+
12RA	M	38	Spices	+	+	-	-	+
			Milk	-	-	-	-	+
13KF	M	32	Apple	+	+	+	+	-
			Potato	-	-	-	-	-
14AC	F	40	Nuts	+	+	-	-	-
			Maize	-	-	-	+	-
15KF	M	38	Nuts	+	-	+	+	-
16TM	F	28	Nuts	+	-	-	-	-
17SJ	F	37	Nuts	+	-	-	-	-
18LS	M	44	Nuts	+	+	-	-	-
			Rice	-	-	-	-	-
19SL	M	29	Wheat flour	+	+	+	-	?
			Potato	-	+	+	-	?

HR: histamine release; no.: number; pat.: patient; H: patients’ history with regard to causative allergens and tolerated foodstuff.

Table 2 Clinical symptoms induced by blinded, placebo-controlled food challenge, atopy status and predominant type of allergy according to Coombs and Gell

Pat. No.	Main symptoms	Atopystatus	Type of allergy
1	Diarrhoea, flush, pruritus	-	Type I (systemic IgE)
2	Abdominal pain, loose stools	+	Type I (systemic IgE)
	bloating
3	Vomiting, diarrhoea	+	Type I (systemic IgE)
4	Abdominal pain, urticaria	-	Type I (local IgE)
5	Diarrhoea, abdominal pain	+	Type I (systemic IgE)
	dyspepsia, vomiting
6	Diarrhoea	-	Type I (systemic IgE)
7	Vomiting, loose stools	+	Type I (systemic IgE)
	right lower quadrant pain
8	Profuse watery diarrhea	-	Type I (systemic IgE)
9	Diarrhoea, bloating, tachy-	+	Type III (immune com-
	cardia		plexes present) or IV (?)
10	Pruritus, Rhinitis, tachycardia	-	Type I (systemic IgE)
	bloating, diarrhoea
11	Colitis, diarrhoea, arthragia	-	Type I (systemic IgE)
	rhinitis
12	Bloody diarrhoea, hypotension,	-	Type I (local IgE) and
	abdominal pain, bloating		/or type III (immune
			complexes present)
13	Fever, diarrhoea, hypotension	+	Type I (systemic IgE)
14	Diarrhoea, vomiting, abdominal	-	Type IV (cellular hyper-
	pain		sensitivity ?)
15	Bloating, diarrhoea, eosinophilia	+	Type I (systemic IgE)
16	Atopic eczema, diarrhoea, colitis,	+	Type I (local IgE) and
	abdominal pain		/or type IV (cellular
			hyper-sensitivity ?)
17	Rhinitis, vomiting, diarrhoea	+	Type I (local IgE)
18	Diarrhoea, bloating	+	Type I (local IgE)
19	Eosinophilia, bloating, diarrhoea	+	Type I (systemic IgE)

Atopy status was defined as positive, when history or clinical manifestation of the patient gave evidence for milk crust, atopic eczema, asthma bronchiale and/or allergic rhino-conjunctivitis. For definition of the allergy type, the most dominant immunological signs were chosen to classify the ongoing allergic mechanisms in this population of patients with manifest gastrointestinally mediated allergy. However, some patients displayed symptoms that suggested more than one definitive type of allergy (see for example patient No. 9, 12, 16): Type I allergy (systemic IgE) was recognised when positive skin or antigen specific IgE levels were present in serum, type I allergy (local IgE) was diagnosed when intestinal lavage fluid contained elevated levels of IgE[20]. Type III allergy was found in patients no. 9 and 12 who showed formation of either IgA, IgM and/or IgE immune complexes during or after allergen application by blinded food challenge. Additionally, type IV allergy was suspected in patients with heightened serum TNF levels during food challenge, and additionally in patient no. 14 who had a positive antigen-specific lymphocyte proliferation test.

Table 3 Results from colorectal mucosal histamine release (% of total tissue histamine content) following ex vivo mucosa oxygenation in patients with GMA

Pat.	Spontaneous	Control		Provocation
No.	HR	Anti-IgE	Allergen	allergen
1	1.7	5.4	3.1	8.7
2	2.6	12.6	11.5	17.3
3	3.4	5.2	4.5	39.1
4	3.2	6.2	-	8.8
5	3.3	6.0	3.1	3.0
6	0.5	3.7	0.9	5.1
7	4.1	1.6	8.9	27.6
8	7.5	2.9	8.3	3.2
9	7.0	6.6	4.9	8.1
10	2.5	3.6	3.0	4.8
11	0.3	3.6	-	1.5
12	1.4	7.9	2.4	11.3
13	5.3	-	3.7	11.2
14	22.4	25.6	20.7	57.9
15	25.8	23.0	-	28.7
16	1.5	-	-	1.8
17	4.8	9.3	-	6.7
18	2.9	3.8	2.8	5.8
19	0.1	1.1	0.4	2.4
Median:	3.20	5.40b	3.40	8.10a
(range)	0.1-25.8	1.1-25.6	0.4-20.7	1.5-57.9

Significance levels:

^aP = 0.008 vs spontaneous histamine release;

^bP = 0.04 vs spontaneous histamine release. HR: histamine release (average value from two measurements); no.: number; pat.: patient; anti-IgE: anti-immunoglobulin E. Control and provocation allergen are allergens, which were either tolerated or induced clinical symptoms during blinded oral food challenge procedures. Rates of histamine release are expressed as percentage (%) of total tissue histamine content. Each release value represents the average value from two repeat experiments (two separate biopsies).

Table 4 Colorectal mucosal histamine release in comparison with the outcome of oral provocation tests in patients with GMA

	Positive HR	Negative HR	Line sum
Positive BPCFC	12	7	19
Negative BPCFC	3	11	14
Column sum	15	18

HR: histamine release, BPCFC: (double- or single) blinded, placebo-controlled oral food challenge. Colorectal mucosal histamine release: Sensitivity 63.1%, specificity 78.6%.

Table 5 Patients’ history in comparison with the outcome of oral provocation tests in patients with GMA

	Positive H	Negative H	Line sum
Positive BPCFC	4	9	13
Negative BPCFC	3	4	7
Column sum	7	13

H: patients’ history, BPCFC: (double- or single) blinded, placebo-controlled oral food challenge. Note: Only 13 of 19 patients (68%) felt confident to answer questions concerning suspected provocation antigens, while the remaining were uncertain or had no experience of adverse reactions to the particular antigen. For evaluation of the specificity of patients’ history, data from only 7 patients (37%) were available. Patients’ history: Sensitivity 30.8%, specificity 57.1%.

Table 6 Skin prick tests in comparison with the outcome of oral provocation tests in patients with GMA

	Positive prick test	Negative prick test	Line sum
Positive BPCFC	9	10	19
Negative BPCFC	3	11	14
Column sum	12	21

BPCFC: (double- or single) blinded, placebo-controlled oral food challenge. Skin prick test: Sensitivity 47.4%; specificity 78.6%.

Table 7 Allergen-specific serum IgE determinations (RAST test) in comparison with the outcome of oral provocation tests in patients with GMA

	Positive RAST	Negative RAST	Line sum
Positive BPCFC	11	8	19
Negative BPCFC	7	7	14
Column sum	18	15

BPCFC: (double- or single) blinded, placebo-controlled oral food challenge. Allergen-specific IgE detection in serum: Sensitivity 57.9%; specificity 50.0%.