The Impact of Human Platelet Antigen Allele on Antiplatelet Antibodies and Cryoglobulins in Patients with Primary Immune Thrombocytopenia and Hepatitis C Virus-Associated Immune Thrombocytopenia.
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Abstract
Background and objectives: Human platelet antigens (HPAs) are alloantigens associated with antiplatelet alloantibodies and the risk of immune thrombocytopenia (ITP). However, few studies have investigated associations among HPAs, antiplatelet autoantibodies, and cryoglobulins.
Methods: We enrolled 43 patients with primary ITP, 47 with hepatitis C virus-associated ITP (HCV-ITP), 21 with hepatitis B virus-associated ITP (HBV-ITP), 25 controls with HCV, and 1013 normal controls. We analyzed HPA allele frequencies, including HPA1-6 and 15, antiplatelet antibodies binding to platelet glycoprotein (GP) IIb/IIIa, Ia/IIa, Ib/IX, IV, human leukocyte antigen class I, cryoglobulin IgG/A/M, and their associations with thrombocytopenia.
Results: In the ITP cohort, HPA2ab, rather than HPA2aa, predicted a low platelet count. HPA2b was associated with the risk of developing ITP. HPA15b was correlated with multiple antiplatelet antibodies. In HCV-ITP patients, HPA3b was correlated with anti-GPIIb/IIIa antibodies. HCV-ITP patients with anti-GPIIb/IIIa antibodies had a higher positive rate of cryoglobulin IgG and IgA compared with those without anti-GPIIb/IIIa antibodies. Overlapping detection was also found among other antiplatelet antibodies and cryoglobulins. Like the antiplatelet antibodies, cryoglobulins were associated with clinical thrombocytopenia, implying their close relationship. Finally, we extracted cryoglobulins to confirm the exhibition of cryoglobulin-like antiplatelet antibodies. In contrast, in primary ITP patients, HPA3b was correlated with cryoglobulin IgG/A/M rather than anti-GPIIb/IIIa antibodies.
Conclusion: HPA alleles were associated with antiplatelet autoantibodies and had different impacts in primary ITP and HCV-ITP patients. HCV-ITP was considered to be a symptom of mixed cryoglobulinemia in HCV patients. The pathophysiology may differ between these two groups.
期刊介绍:
Reciprocal interdependence between infectious and hematologic diseases (malignant and non-malignant) is well known. This relationship is particularly evident in Mediterranean countries. Parasitosis as Malaria, Leishmaniosis, B Hookworms, Teniasis, very common in the southeast Mediterranean area, infect about a billion people and manifest prevalently with anemia so that they are usually diagnosed mostly by experienced hematologist on blood or bone marrow smear. On the other hand, infections are also a significant problem in patients affected by hematological malignancies. The blood is the primary vector of HIV infection, which otherwise manifest with symptoms related to a reduction in T lymphocytes. In turn, infections can favor the insurgency of hematological malignancies. The causative relationship between Epstein-Barr virus infection, Helicobacter pylori, hepatitis C virus, HIV and lymphoproliferative diseases is well known.