Molecular typing of human platelet antigens in immune thrombocytopenia patients in northern Brazil

Carmo, Julia Cavalcante do; Klippel, Prissyla de Souza; Cordeiro, Sabrine da Costa; Fernandes, Ângela Maria dos Santos; Pinto, Raquel Medeiros; Weber, Simone Schneider; Fantin, Cleiton

doi:10.1016/j.bjhh.2017.01.003

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Revista Brasileira de Hematologia e Hemoterapia

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Original Articles • Rev. Bras. Hematol. Hemoter. 39 (2) • Apr-Jun 2017 • https://doi.org/10.1016/j.bjhh.2017.01.003 copy

Molecular typing of human platelet antigens in immune thrombocytopenia patients in northern Brazil

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Background:

Immune thrombocytopenia is an immune disease characterized by thrombocytopenia and bleeding due to platelet antibodies against platelet membrane glycoproteins. Human platelet antigens are derived from polymorphisms of these glycoproteins. The aim of this study was to investigate human platelet antigen frequencies in immune thrombocytopenia patients from the state of Amazonas, Brazil and investigate the potential association between specific antigens and risk for immune thrombocytopenia.

Method:

Human platelet antigen typing was performed by BeadChip technology to determine allelic variants of 11 systems (HPA-1 to HPA-9, HPA-11 and HPA-15). Thirty-six patients (8 male and 28 female) with a median age of 34 years (range: 9-69 years) were evaluated and compared with data from Amazonas blood donors.

Results:

Platelet counts varied from 3 to 98 × 10⁹/L. The allele frequencies were 0.944 for HPA-1a, 0.056 for HPA-1b, 0.847 for HPA-2a, 0.153 for HPA-2b, 0.555 for HPA-3a, 0.444 for HPA-3b, 0.805 for HPA-5a, 0.222 for HPA-5b, 0.9975 for HPA-9a, 0.025 for HPA-9b, 0.486 for HPA-15a and 0.513 for HPA-15b. Among immune thrombocytopenia individuals, no b allele of the HPA-4, -6, -7, -8 and -11 were found.

Conclusions:

The results suggest HPA-1a, HPA-3b and HPA-5b are immune thrombocytopenia-specific autoepitopes.

Keywords:
Immune thrombocytopenia; Platelets; BeadCheap technology; Genotyping; HPA

Clinical data		ITP patients		Blood donors^b b Control includes blood donor samples published by Portela et al.19
n° patients		36		200
Gender (male:famale)		8:28		140:60
Age (years)		34 (9-69)		36 (19-65)
Platelet count - ×10⁹/L		41.5 (3-98)^a a Platelet count at diagnosis.		>150^c c Platelet counts greater than 150 × 109/L.
System	a	b	a	b	p-value^d d Chi-square with Yates’ correction calculated Fisher's exact p-value for comparisons of allele frequencies between ITP patients and Amazonas blood donors.
HPA-1	0.944	0.056	0.86	0.137	<0.0001
HPA-2	0.847	0.153	0.852	0.147	0.754
HPA-3	0.555	0.444	0.665	0.335	<0.0001
HPA-4	1.00	0.00	0.995	0.005	<0.0001
HPA-5	0.805	0.222	0.892	0.107	<0.0001
HPA-6	1.00	0.00	1.00	0.00	-
HPA-7	1.00	0.00	1.00	0.00	-
HPA-8	1.00	0.00	1.00	0.00	-
HPA-9	0.997	0.025	0.997	0.005	-
HPA-11	1.00	0.00	1.00	0.00	-
HPA-15	0.486	0.513	0.502	0.497	0.502

	GP	SNP	Genotype frequency			Allele frequency		p-value Hardy-Weinberg
			AA	AB	BB	a	b
HPA-1	GPIIIa	T176C	0.888	0.111	0.00	0.944	0.056	0.724
HPA-2	GPIIa	T482C	0.694	0.305	0.00	0.847	0.153	0.279
HPA-3	GPIIb	T2621G	0.305	0.5	0.194	0.555	0.444	0.940
HPA-4	GPIIIa	G506A	1.00	0.00	0.00	1.0	0.00	-
HPA-5	GPIa	G1600G	0.611	0.388	0.027	0.805	0.222	0.479
HPA-6	GPIIIa	G1544A	1.00	0.00	0.00	1.0	0.00	-
HPA-7	GPIIIa	C1297G	1.00	0.00	0.00	1.0	0.00	-
HPA-8	GPIIIa	C1984T	1.00	0.00	0.00	1.0	0.00	-
HPA-9	GPIIb	G2602A	0.995	0.005	0.00	0.9975	0.025	0.97
HPA-11	GPIIIa	G1976A	1.00	0.00	0.00	1.0	0.00	-
HPA-15	CD109	C2108A	0.166	0.638	0.194	0.486	0.513	0.094

Systems	Gd_AA	Gd_AB	Gd_BB	Mismatch in AA patients	95% confidence interval		Mismatch BB patients	95% confidence interval
				Gd_AB + Gd_BB (%)	Lower limit	Upper limit	Gd_AB + Gd_AA (%)	Lower limit	Upper limit
HPA-1	0.740	0.245	0.015	0.26 (26)	0.227	0.292	0.98 (98)	0.915	1.00
HPA-2	0.720	0.265	0.015	0.28 (28)	0.244	0.315	0.98 (98)	0.921	1.00
HPA-3	0.430	0.470	0.100	0.57 (57)	0.518	0.621	0.90 (90)	0.894	0.905
HPA-4	0.990	0.010	0.000	0.01 (1)	0.008	0.011	1.00 (100)	0.862	1.00
HPA-5	0.800	0.185	0.015	0.20 (20)	0.176	0.223	0.98 (98)	0.898	1.00
HPA-9	0.995	0.005	0.000	0.005 (0.5)	0.004	0.005	1.00 (100)	0.861	1.00
HPA-15	0.252	0.495	0.250	0.745 (75)	0.710	0.779	0.747 (75)	0.712	0.781

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[1] *Corresponding author at: Centro de Ciências Biológicas e da Saúde. Universidade Federal do Mato Grosso do Sul, Cidade Universitária S/N, Caixa Postal 549, 79070-900 Campo Grande, MS, Brazil. E-mail address: weberblood@gmail.com (S.S. Weber)