Differentiation of autoimmune thrombocytopenia from thrombocytopenia associated with immune complex disease: systemic lupus erythematosus, hepatitis‐cirrhosis, and HIV‐1 infection by platelet and serum immunological measurements

Abstract

Summary.A method and approach are described to differentiate classic autoimmune thrombocytopenia (ATP) from immune complex-associated thrombocytopenia in systemic lupus (SLE), hepatitis/chronic liver disease (LIV-ITP) and HIV-1 related thrombocytopenia (HIV-1-ITP). The platelet immunologic profile of IgG, C3C4 and IgM was measured with a solid-phase ELISA, employing 125 I-staphylococcal protein A to detect indicator antibody binding. Polyethylene glycol was employed to precipitate immune complexes (PEG-IC). Platelet-associated IgG (PAIgG) was 2·8-, 5·6-and 5·8-fold higher in SLE, LIV-ITP and HIV-1-ITP patients respectively compared to ATP patients; platelet C3C4 was 3·2-, 4·8-and 4·5-fold higher respectively; platelet IgM was 2·2-, 3·7-and 3·8-fold higher respectively; serum PEG-IC levels were 4·2-, 4·8-and 2·1-fold higher respectively. With all parameters measured, there was no overlap between the 75th percentile for ATP patients and the 25th percentile for all three cohorts. The likelihood of having a platelet C3C4 level higher than the highest ATP level was 69% for SLE, 90% for LIV-ITP and 94% for HIV-1-ITP respectively; with PEG-IC measurements the likelihood was 83%, 100% and 100% respectively. Serum IgG, C3, C4, IgM and PEG-IC were examined for a possible relationship with platelet measurements. Except for a positive correlation between serum and platelet IgM in ATP, r ¼ 0·5, P < 0·04, there was no positive correlation with any of the parameters measured. An inverse correlation was noted between PEG-IC level and platelet C3C4 in SLE, r ¼ 0·7, P < 0·04. Thus platelet immunologic profile and serum PEG-IC level measurements differentiated classic ATP from immune complex-associated thrombocytopenias (SLE, LIV-ITP, HIV-1-ITP). Except for IgM measurements in ATP, platelet measurements could not be attributed to their respective serum concentration.

Role of molecular mimicry of hepatitis C virus protein with platelet GPIIIa in hepatitis C–related immunologic thrombocytopenia

“…We consider this debatable because of patients whom we have studied with severe liver cirrhosis who had abundant IgG on their platelets as well as in their immune complexes. 16 It is of interest that both HCV and HIV-1 each contain different structural elements that mimic peptide sequences in GPIIIa49-66 and that both viruses are capable of inducing GPIIIa49-66-specific antibodies capable of causing thrombocytopenia. A possible explanation is that both the HCV and HIV-1 mimicry epitopes are in nonconserved highly mutated regions of the 2 viruses, and that mimicry of host proteins serves to help viruses escape host immune surveillance.…”

“…14 Patients with HCV commonly develop immunologic thrombocytopenia (HCV-ITP) that correlates with severity of disease (eg, chronic active hepatitis, cirrhosis). [15][16][17] The incidence of HCV-ITP in a series of 368 HCV Japanese patients with chronic persistent or chronic active hepatitis was 41%. The incidence of endemic HCV-ITP in 294 chronic patients was 10%, which increased to 32% with advanced liver disease.…”

“…Like HIV-1-ITP, patients with HCV-ITP have increased serum immune complexes. 16 We therefore reasoned that a second autoimmune disease with serum immune complex associated immunologic thrombocytopenia could also contain an anti-GPIIIa49-66 Ab capable of inducing oxidative platelet fragmentation-induced by molecular mimicry with an HCV peptide in addition to HIV nef peptide in HIV-1-ITP. 15 In the present report, we demonstrate the following: (1) four HCV core-envelope peptides from a nonconservative region display molecular mimicry with GPIIIa49-66 by reactivity with anti-GPIIIa49-66 Ab.…”

Thrombocytopenia in malaria: who cares?

“…More recently, molecular mimicry was proposed between nef HIV-1 protein and GPIIIa [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66] (Li et al 2005) . Other chronic infectious diseases known to cause thrombocytopenia include chronic viral hepatitis, where CIC (Samuel et al 1999) and PAIgG (Doi et al 2002) are also implicated. In the case of hepatitis C virus infection, the blockage in the maturation of megakaryocytes is mediated by the viral RNA itself (Almeida 2003).…”

SLE Thrombocytopenia: From Peripheral Platelet Destruction to Central Hemopoietic Defect

“…Finally, AITP patients show evidence that autoantibody production is mediated through the oligoclonal expansion of B-cells after exposure to platelet antigens, using genetically predetermined and specific rearrangements of heavy and light chain genes [62]. These characteristics are not evident in SLE, suggesting that SLE thrombocytopenia is not a direct immunologic response against platelets and therefore not a true AITP [63]. Even though antiplatelet antibodies remain an acceptable mechanism of platelet destruction [64], other mechanisms have attracted attention.…”