Transient Antibodies Research Articles

P0718 DARWIN'S ILLNESS: A FASCINATING PROBLEM FOR INTERNAL MEDICINE

P0717 – Table 1 Communication Virus Diagnosis Symptoms Predisposing factor Management Outcome Suzuki et al. EBV CT scan, pathology. Fever, icterus, left upper quadrant abdominal pain and tenderness. Hereditary spherocytosis Analgesia, antibiotics, splenectomy 2 months later. Cured Breuer et al. EBV CT scan Fever, left upper quadrant pain and abdominal tenderness. Hereditary spherocytosis, Protein C deficiency. Analgesia, antibiotics. Cured Ofotokun et al. CMV CT scan, pathology. Fever, Abdominal pain, rigors and diaphoresis. None Ganciclovir, splenectomy, thrombolisis Cured Benz et al. EBV CT scan Fever, tonsillitis, generalized lymphadenopathy and left pleuritic chest pain. None Acetaminphen Cured Van Haal et al. EBV CT scan Fever, generalised myalgias and abdominal pain with upper left quadrant tenderness. Transient antiphospholipid antibodies. Support therapy Cured Symeonidis et al. EBV CT scan Fever, upper respiratory tract infection symptoms, left upper quadrant pain, nausea and vomiting. Sickle cell trait Support therapy Cured Trevenzoli et al. EBV CT scan Fever, pharyngitis, left upper quadrant pain. None Support therapy Cured Guibaud et al EBV Clinically and confirmed after surgery. Violent pain in left hipocondria. Transient neutrophil aggregation, Elevated quantity of immune complexes. Splenectomy Cured Garten et al EBV CT scan Fever, chills, malaise and night sweats. None Splenectomy (made for diagnosis, lymphoma was suspected) Cured Boivin et al EBV Ecography Fever, jaundice, left upper quadrant abdominal pain. Pyruvate kinase deficiency, haemolytic anemia cold autoantibodies. Splenectomy Cured

IFNα kinoid vaccine-induced neutralizing antibodies prevent clinical manifestations in a lupus flare murine model

A major involvement of IFNalpha in the etiopathogenesis of systemic lupus erythematosus has been suggested by clinical observations, including the increase of serum levels of this cytokine in patients with active disease. Supporting this hypothesis, we have shown that expression of IFNalpha from a recombinant adenovirus (IFNalpha Adv) precipitates lupus manifestations in genetically susceptible New Zealand Black (NZB) x New Zealand White (NZW)F(1) mice (NZB/W) but not in BALB/c mice. In the present investigation, we have prepared an IFNalpha immunogen, termed IFNalpha kinoid, which, appropriately adjuvanted, induces transient neutralizing antibodies (Abs) but no cellular immune response to the cytokine and without apparent side effects. Using this preparation, we also showed that, in kinoid-vaccinated NZB/W mice, lupus manifestations, including proteinuria, histological renal lesions, and death triggered by IFNalpha Adv challenge were delayed/prevented as long as an effective threshold of anti-IFNalpha inhibitory capacity was present in the serum.

Bilateral cavo-ilio-femoral thrombosis in an adolescent with transient anti-phospholipid antibodies and Factor V heterozygous mutation: a case report

We report a case of bilateral cavo-ilio-femoral thrombosis in an adolescent with factor V heterozygous mutation and transient antiphospholipid antibodies secondary Varicella infection.The clinical significance of finding transient antiphospholipid antibodies in the sera of infectious disease is unclear. We here report a case of bilateral cavo-ilio-femoral thrombosis in an adolescent with newly diagnosed factor V heterozygous mutation and transient antiphospholipid antibodies secondary to Varicella infection.

Transient human anti-mouse antibodies (HAMA) interference in CA 125 measurements during monitoring of ovarian cancer patients treated with murine monoclonal antibody

Objective To investigate the influence of human anti-mouse antibodies (HAMA) on serial CA 125 measurements in serum of patients with epithelial ovarian cancer following single intraperitoneal (IP) therapy with Yttrium-90-labeled human milk fat globule 1 murine monoclonal antibody ( 90Y-muHMFG1) as part of a large international randomized phase III trial. Methods We monitored CA 125 concentrations in longitudinally collected serum samples from 224 patients after IP 90Y-muHMFG1 (study group) and from 223 patients who received standard treatment (control group). Serum samples of 22 study patients with increased CA 125 concentrations were selected and subjected to affinity chromatography to study HAMA interference in CA 125 measurements. Results CA 125 serum concentrations at weeks 1, 4 and 8 were significantly higher in the study group than in the control group. In the first 8 weeks after IP 90Y-muHMFG1 administration significantly more patients of the study group (144/224) demonstrated CA 125 concentrations above the upper limit of normal of 23 U/mL, as compared to those of the control group (37/223). Affinity chromatography of serum with high CA 125 values in the first 8 weeks confirmed HAMA interference in CA 125 measurements while after 24 weeks this HAMA interference could no longer be detected. Conclusions This is the first study to demonstrate that clinical trials applying murine monoclonal antibodies may be flawed by a transient HAMA effect, which should be considered when monitoring ovarian cancer patients with CA 125 measurements.

Reticulate keloidal purpura associated with transient antiphospholipid antibodies and hyperhomocysteinaemia

A 66-year-old woman presented with a reticulate pattern of purpuric, keloidal scarring affecting her lower legs and necrosis of her left thumb and little finger as sequelae of an episode of staphylococcal septicaemia. Her premorbid past history includes three miscarriages, three episodes of pulmonary embolism and an internal iliac vein thrombosis. Skin biopsy specimens showed keloidal scar tissue in the dermis but no evidence of thrombosis or vasculitis. Blood tests demonstrated moderate hyperhomocysteinaemia. Elevated levels of anticardiolipin antibodies were found on one occasion but this was not detected on initial or repeat testing.

Mycoplasma pneumoniae, Splenic Infarct, and Transient Antiphospholipid Antibodies: A New Association?

We report 2 children with Mycoplasma pneumoniae pulmonary infection with splenic infarcts and transient antiphospholipid antibodies. This association has not been reported previously.

7B.2 Antiphospholipid syndrome: clinical manifestations and treatment

Clinical manifestations Antiphospholipid syndrome has a heterogeneous clinical presentation and, consequently, may be encountered by clinicians in a range of specialties. Thrombosis of the deep limb veins, sometimes with pulmonary embolism, is a common first manifestation. However any region of the venous system can be involved including superficial, mesenteric, portal, intracranial and retinal veins. The characteristic serological feature of the syndrome is the presence of antiphospholipid antibody, typically lupus inhibitor and/or anticardiolipin/anti-b2-glycoprotein I antibody. Depending on the composition of the population examined around 3% of patients with a first DVT are positive for lupus inhibitor. Arterial thrombosis occurs also. Ischaemic stroke is the commonest manifestation, but myocardial infarction, peripheral gangrene and thrombotic occlusion of any part of the arterial tree, including mesenteric, adrenal and renal vessels, can occur. Occasionally, clinical manifestations can be ascribed to involvement of the microvasculature, for example renal impairment and seizures. “Catastrophic antiphospholipid syndrome” is an acute, dramatic and life-threatening form of thrombotic microangiopathy affecting multiple organs. Kidneys, lungs, skin and central nervous system are frequently involved. Fortunately this presentation is encountered exceedingly uncommonly. Other reported manifestations of antiphospholipid syndrome include skin lesions (typically livedo reticularis but also ulceration), cardiac valve lesions (ranging from valve thickening to sterile endocarditis with vegetations), non-stroke neurological manifestations (such as sensori/neural deafness, chorea, cognitive impairment and multifocal ischaemia mimicking demyelinating disease) and consumptive haematological cytopenias (autoimmune haemolytic anaemia and thrombocytopenia). Pregnancy failure and maternal morbidity are well recognized manifestations of antiphospholipid syndrome. Recurrent miscarriage, fetal growth retardation, fetal death and severe (often early) pre/eclampsia may occur. In many women these are the only manifestations, health remaining good when non-pregnant. Placental thrombosis may explain some of these events but alternative mechanisms probably account for very early pregnancy failure. In some cases antiphospholipid syndrome complicates established connective tissue disease, classically systemic lupus erythematosus, but in many others thrombosis or pregnancy failure is the only feature. The diagnosis of antiphospholipid syndrome may be problematic because of the high background prevalence of arterial and venous thrombosis in adults, as well as the common phenomenon of transient antiphospholipid antibodies which are often associated with self-limiting infections and are not usually associated with thrombotic events. Furthermore antiphospholipid antibodies occur in some chronic infections (classically syphilis but also chronic viral infections including hepatitis C and HIV) and iatrogenically, for example due to phenothiazine treatment. Again, thrombosis is not usually a feature in these circumstances. Diagnostic uncertainty is exacerbated by the poor performance and unreliability of the laboratory tests for antiphospholipid antibodies. Furthermore, low titre anticardiolipin antibodies are a frequent finding in the general population and are of uncertain significance.

Isolation of a 14 kDa antigen from Taenia solium cyst fluid by HPLC and its evaluation in enzyme linked immunosorbent assay for diagnosis of porcine cysticercosis

A fraction with a major band of 14 kDa was obtained from crude cyst fluid of Taenia solium cysticerci by 2-step chromatography. A first fraction isolated by gel filtration (Sephacryl S-300 high resolution) was purified using an anion exchange column (Mono Q HR 5/5) on high performance liquid chromatography. Evaluation of the analytic sensitivity of this fraction (F3) was carried out in an antibody enzyme linked immunosorbent assay (Ab-ELISA-F3) using serum samples from pigs experimentally infected with different doses of T. solium eggs. The cross-reactivity of F3 was evaluated with serum samples from pigs that were naturally or experimentally infected with Taenia hydatigena, Taenia saginata asiatica, Fasciola hepatica, Trichinella spiralis, Metastrongylus apri, Trypanosoma congolense and Sarcoptes scabiei, and with serum samples of rabbits hyper-immunised with metacestode cyst fluid of T. hydatigena and T. solium. Antibody titres of lightly or heavily infected pigs differed in their kinetics. However, the increase in F3-specific antibodies could not be related to the infection level. Analysis of the specificity of the F3 showed that serum samples of pigs infected with other parasites did not recognise this antigen. Cross-reaction with T. hydatigena occurred in ELISA using cyst fluid as antigen, but the F3 antigen fraction was not recognized by rabbit hyper-immune serum samples to T. hydatigena. Evaluation of the diagnostic sensitivity and specificity of the Ab-ELISA-F3 was done by a non-parametric receiver operating characteristic (ROC) analysis using 66 serum samples from Zambian village pigs. The total number of cysticerci of these pigs was determined by dissection (28 pigs harboured T. solium cysticerci and 38 were negative at dissection). In addition, 58 serum samples from Cameroonian pigs (28 pigs from cysticercosis-free farms and 30 pigs with cysticerci at tongue inspection) were used in a separate ROC analysis. The results from the ROC analysis yielded a low diagnostic value (area under ROC curve = 0.48) with the sera from the Zambian pigs while a relatively high diagnostic value was obtained with the sera from Cameroonian pigs (area under ROC curve = 0.78). The main factor contributing to a low diagnostic value based on the Zambian serum samples seemed to be the false-positive reactions that were likely caused by the occurrence of transient antibodies in the non-infected animals.

Immunomodulation of transgene responses following naked DNA transfer of human factor VIII into hemophilia A mice

A robust humoral immune response against human factor VIII (hFVIII) following naked DNA transfer into immunocompetent hemophilia A mice completely inhibits circulating FVIII activity despite initial high-level hFVIII gene expression. To prevent this undesirable response, we compared transient immunomodulation strategies. Eight groups of mice (n = 4-9 per group) were treated with naked DNA transfer of pBS-HCRHPI-hFVIIIA simultaneously with immunosuppressive reagents that included cyclosporine A (CSA), rapamycin (RAP), mycophenylate mofetil (MMF), a combination of CSA and MMF, a combination of RAP and MMF, a monoclonal antibody against murine CD40 ligand (MR1), recombinant murine Ctla4Ig, and a combination of MR1 and Ctla4Ig. All animals except those receiving only CSA exhibited delayed or absent immune responses against hFVIII. The most effective immunosuppressive regimen, the combination of Ctla4Ig and MR1, prevented inhibitor formation in 8 of 9 animals; the ninth had transient low-titer antibodies. All 9 mice of this group produced persistent, therapeutic levels of hFVIII for more than 6 months. When challenged with the T-dependent antigen bacteriophage Phix174, tolerized mice exhibited normal primary and secondary antibody responses, suggesting that transient immunomodulation to disrupt B/T-cell interaction at the time of plasmid injection effectively promoted long-term immune tolerance specific for hFVIII.

RECOMBINANT HUMAN BMP-2 AND ALLOGRAFT COMPARED WITH AUTOGENOUS BONE GRAFT FOR RECONSTRUCTION OF DIAPHYSEAL TIBIAL FRACTURES WITH CORTICAL DEFECTS

Background: Currently, the treatment of diaphyseal tibial fractures associated with substantial bone loss often involves autogenous bone-grafting as part of a staged reconstruction. Although this technique results in high healing rates, the donor-site morbidity and potentially limited supply of suitable autogenous bone in some patients are commonly recognized drawbacks. The purpose of the present study was to investigate the benefit and safety of the osteoinductive protein recombinant human bone morphogenetic protein-2 (rhBMP-2) when implanted on an absorbable collagen sponge in combination with freeze-dried cancellous allograft. Methods: Adult patients with a tibial diaphyseal fracture and a residual cortical defect were randomly assigned to receive either autogenous bone graft or allograft (cancellous bone chips) for staged reconstruction of the tibial defect. Patients in the allograft group also received an onlay application of rhBMP-2 on an absorbable collagen sponge. The clinical evaluation of fracture-healing included an assessment of pain with full weight-bearing and fracture-site tenderness. The Short Musculoskeletal Function Assessment (SMFA) was administered before and after treatment. Radiographs were used to document union, the presence of extracortical bridging callus, and incorporation of the bone-graft material. Results: Fifteen patients were enrolled in each group. The mean length of the defect was 4 cm (range, 1 to 7 cm). Ten patients in the autograft group and thirteen patients in the rhBMP-2/allograft group had healing without further intervention. The mean estimated blood loss was significantly less in the rhBMP-2/allograft group. Improvement in the SMFA scores was comparable between the groups. No patient in the rhBMP-2/allograft group had development of antibodies to BMP-2; one patient had development of transient antibodies to bovine type-I collagen. Conclusions: The present study suggests that rhBMP-2/allograft is safe and as effective as traditional autogenous bone-grafting for the treatment of tibial fractures associated with extensive traumatic diaphyseal bone loss. Level of Evidence: Therapeutic Level II. See Instructions to Authors for a complete description of levels of evidence.

Recombinant Human BMP-2 and Allograft Compared with Autogenous Bone Graft for Reconstruction of Diaphyseal Tibial Fractures with Cortical Defects

Currently, the treatment of diaphyseal tibial fractures associated with substantial bone loss often involves autogenous bone-grafting as part of a staged reconstruction. Although this technique results in high healing rates, the donor-site morbidity and potentially limited supply of suitable autogenous bone in some patients are commonly recognized drawbacks. The purpose of the present study was to investigate the benefit and safety of the osteoinductive protein recombinant human bone morphogenetic protein-2 (rhBMP-2) when implanted on an absorbable collagen sponge in combination with freeze-dried cancellous allograft. Adult patients with a tibial diaphyseal fracture and a residual cortical defect were randomly assigned to receive either autogenous bone graft or allograft (cancellous bone chips) for staged reconstruction of the tibial defect. Patients in the allograft group also received an onlay application of rhBMP-2 on an absorbable collagen sponge. The clinical evaluation of fracture-healing included an assessment of pain with full weight-bearing and fracture-site tenderness. The Short Musculoskeletal Function Assessment (SMFA) was administered before and after treatment. Radiographs were used to document union, the presence of extracortical bridging callus, and incorporation of the bone-graft material. Fifteen patients were enrolled in each group. The mean length of the defect was 4 cm (range, 1 to 7 cm). Ten patients in the autograft group and thirteen patients in the rhBMP-2/allograft group had healing without further intervention. The mean estimated blood loss was significantly less in the rhBMP-2/allograft group. Improvement in the SMFA scores was comparable between the groups. No patient in the rhBMP-2/allograft group had development of antibodies to BMP-2; one patient had development of transient antibodies to bovine type-I collagen. The present study suggests that rhBMP-2/allograft is safe and as effective as traditional autogenous bone-grafting for the treatment of tibial fractures associated with extensive traumatic diaphyseal bone loss. Therapeutic Level II. See Instructions to Authors for a complete description of levels of evidence.

Brain and optic nerve ischemia in malaria with immune disorders

We report an unusual case of Plasmodium falciparum malaria in a European returning from tropical regions associating an anterior ischemic optic neuropathy and an asymptomatic centropontine myelinolysis. The transient antiphospholipid antibodies detected in the patient may have played a role in the ischemic process at the origin of this unusual clinical association.

Transient antiphospholipid antibodies associated with acute infections in children: a report of three cases and a review of the literature

We describe two previously healthy children who had multiple ecchymoses several days after acute infection. In both cases, the prothrombin time (PT) and the activated partial thromboplastin time (APTT) were prolonged. Further examinations revealed the presence of lupus anticoagulant (LA), phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT), and low serum complement. In both cases, we confirmed the presence of a serum immune complex. The patients' symptoms improved spontaneously within 1 week, and all laboratory data normalized within several months. We also describe another asymptomatic case positive for LA and aPS/PT presumably associated with cytomegalovirus infection. The prevalence of transient antiphospholipid antibodies associated with viral infections in children must be much higher than we expected. We have to take it into consideration when we see abnormal coagulation results, but the occurrence of significant bleeding symptoms is rare.

Multiple small pulmonary emboli associated with transient antiphospholipid syndrome in human Parvovirus B19 infection

Antiphospholipid antibodies (aPL) have been reported to occur in several conditions other than antiphospholipid syndrome, including infections. We herein report the case of a 21-year-old Japanese woman with Parvovirus B19 infection, who developed multiple pulmonary emboli associated with aPL, a lupus anticoagulant and IgM anticardiolipin antibody. Eight weeks later, antiphospholipid antibodies spontaneously disappeared and normal pulmonary flow was observed. Considering the high prevalence of Parvovirus B19 infection, we should be aware of thrombosis associated with transient aPL antibodies in this infectious disease.

Prolonged aPTT after kidney transplantation due to transient lupus anticoagulants

After kidney transplantation, a renal biopsy may be needed to elucidate the reasons for lack of graft function. If the activated partial thromboplastin time (aPTT) is prolonged, the biopsy will often be postponed, as increased risk of bleeding must be expected. However, aPTT prolongation is not always due to lack of coagulation factors, but can be due to the presence of lupus anticoagulants (LAs). Clinical observations in our department indicated that a large proportion of recently kidney-transplanted patients developed prolonged aPTT values without clinical complications. A prospective study of patients receiving a kidney transplant in 2004 was conducted to investigate the frequency and cause of prolongation of the aPTT. Twenty-seven patients were included in the study; none had prolonged aPTT or LAs before the transplantation. In the post-transplantation period, 19 patients (70.4%) had a significantly prolonged aPTT. Further investigation showed that for all 19 patients, prolongation was due to acquired antibodies: 13 had developed LAs and six had developed unspecific antibodies. The acquired antibodies were transient and did not affect clinical outcome. This is the first study investigating prolonged aPTT in the post-transplantation period. All patients with prolonged aPTT had acquired transient antibodies, i.e. LA or 'LA-like'. If a renal biopsy was requested, 70.4% of the transplanted patients would presumably have their biopsy postponed due to prolonged aPTT, but as LAs do not increase the risk of bleeding, such a delay would be unnecessary. Immediate LA investigation is therefore recommended if a recently transplanted patient requiring surgical procedures has a prolonged aPTT.

Predictive value of persistent versus transient antiphospholipid antibody subtypes for the risk of thrombotic events in pediatric patients with systemic lupus erythematosus

Study objectives were to determine, in children with systemic lupus erythematosus (SLE), (1) the association of antiphosholipid antibody (APLA) subtypes with thrombotic events (TEs) and (2) the predictive value of persistent versus transient antibodies for TEs. This is a cohort study of 58 SLE children in whom lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), anti-beta2-glycoprotein-I (anti-beta2-GPI), and antiprothrombin (anti-PT) were assessed on at least 2 occasions (more than 3 months apart). Antibodies were classified as persistent (positive on at least 2 occasions) or transient (positive once). Outcomes were symptomatic TEs confirmed by objective radiographic tests identified retrospectively and prospectively. Seven of the 58 patients (12%) had 10 TEs; 5 patients had TEs during prospective follow-up. Persistent LAs showed the strongest association with TEs (P < .001). Persistent ACLAs (P = .003) and anti-beta2-GPI (P = .002) were significantly associated with TEs; anti-PT (P = .063) showed a trend. Persistent or transient LAs and anti-beta2-GPI showed similar strength of association, while ACLAs and anti-PT were no longer associated with TEs. Positivity for multiple APLA subtypes showed stronger associations with TEs than for individual APLA subtypes because of improved specificity. Lupus anticoagulant is the strongest predictor of the risk of TEs; other APLA subtypes provide no additional diagnostic value. Anticardiolipin antibodies and anti-PT require serial testing because only persistent antibodies are associated with TEs.

Immunomodulation of Transgene Responses Following Naked DNA Transfer of Factor VIII into Hemophilia A Mice.

Naked DNA transfer of liver-specific, high-expressing plasmid pBS-HCRHPI-FVIIIA in Rag2(−/ −) SCID mice produced persistent high-level gene expression of human factor VIII (hFVIII) (Miao, Hum. Gene Ther. 2003). However, in immunocompetent hemophilia A mice, a robust humoral immune response against FVIII that followed gene transfer led to complete inhibition of circulating FVIII activity (Ye, Mol. Ther. 2004). Transient immunomodulation strategies were explored to prevent the formation of inhibitory antibody formation. Eight groups of mice (n=8) were treated by naked DNA transfer of plasmid pBS-HCRHPI-FVIIIA. Each group were subjected to treatment with single or combined immunosuppressive regimen: CyclosporineA (CSA) daily for 14 days; Rapamycin daily for 14 days; Mycophenylate mofetil (MMF) daily for 14 days; combination of CSA and MMF; combination of Rapamycin and MMF; a monoclonal antibody (MR1) against murine CD40 ligand on days -1, 1, 2, 7, & 14; recombinant murine Ctla4Ig on days 1 & 2; and combination of MR1 and Ctla4Ig. Combination regimens were given using the same combined schedule and dosages. All animals treated with immunosuppression had delayed or no immune responses against hFVIII except the group treated with CSA only. The most effective treatment was observed in animals treated with the combination of Ctla4Ig and MR1. Seven of 8 animals failed to develop detectable inhibitors. One animal developed transient low-titer antibodies. This group of animals produced persistent, therapeutic levels of hFVIII gene expression for over 6 months. Tolerized animals were subsequently challenged by the T dependent antigen, bacteriophage Φx174, and exhibited a normal primary and secondary response including amplification and isotype switch. These results strongly suggest that transient immunomodulation strategies to disrupt B- and T- cell interactions at the time of plasmid injection is effective to promote long-term immune tolerance that is specific for FVIII without altering subsequent immune responses to other T cell dependent antigens.

Synaptic activation of transient receptor potential channels by metabotropic glutamate receptors in the lateral amygdala

Classical mammalian transient receptor potential channels form non-selective cation channels that open in response to activation of phospholipase C-coupled metabotropic receptors, and are thought to play a key role in calcium homeostasis in non-excitable cells. Within the nervous system transient receptor potential channels are widely distributed but their physiological roles are not well understood. Here we show that in the rat lateral amygdala transient receptor potential channels mediate an excitatory synaptic response to glutamate. Activation of group I metabotropic glutamate receptors on pyramidal neurons in the lateral amygdala with either exogenous or synaptically released glutamate evokes an inward current at negative potentials with a current voltage relationship showing a region of negative slope and steep outward rectification. This current is blocked by inhibiting G protein function with GTP-β-S, by inhibiting phospholipase C or by infusing transient receptor potential antibodies into lateral amygdala pyramidal neurons. Using RT-PCR and Western blotting we show that transient receptor potential 1, transient receptor potential 4 and transient receptor potential 5 are present in the lateral amygdala. Single cell PCR confirms the presence of transient receptor potential 1 and transient receptor potential 5 in pyramidal neurons and we show by co-immunoprecipitation that transient receptor potential 1 and transient receptor potential 5 co-assemble as a heteromultimers in the amygdala. These results show that in lateral amygdala pyramidal neurons synaptically released glutamate activates transient receptor potential channels, which we propose are likely to be heteromultimeric channels containing transient receptor potential 1 and transient receptor potential 5/transient receptor potential 4.

Evidence of HIV exposure and transient seroreactivity in archived HIV-negative severe hemophiliac sera

BackgroundApproximately 25% of hemophiliacs that were frequently exposed to blood clotting factor concentrates (CFCs) contaminated with human immunodeficiency virus (HIV) are presently HIV seronegative. In this study, we sought to determine if some of these individuals were at any time transiently HIV seropositive. In the early to mid-1980s the majority of severe hemophilia patients were exposed to CFCs contaminated with HIV. Although many of these hemophiliacs became HIV-positive, a small percentage did not become infected. To determine if some of these individuals successfully resisted viral infection, we attempted to document the presence of transient HIV reactive antibodies in archived plasma samples (1980–1992) from currently HIV-negative severe hemophiliacs who had a high probability of repeated exposure to HIV contaminated CFC. Archived plasma samples were retrospectively tested using an FDA approved HIV-1Ab HIV-1/HIV-2 (rDNA) enzyme immunoassay (EIA) and a HIV-1 Western blot assay (Wb), neither of which were commercially available until the late 1980s, which was after many of these samples had been drawn.ResultsWe found that during the high risk years of exposure to HIV contaminated CFC (1980–1987), low levels of plasma antibodies reactive with HIV proteins were detectable in 87% (13/15) of the haemophiliacs tested. None of these individuals are presently positive for HIV proviral DNA as assessed by polymerase chain reaction (PCR).ConclusionOur data suggest that some severe hemophiliacs with heavy exposure to infectious HIV contaminated CFC had only transient low-level humoral immune responses reactive with HIV antigens yet remained HIV-negative and apparently uninfected. Our data supports the possibility of HIV exposure without sustained infection and the existence of HIV-natural resistance in some individuals.

Splenic infarction due to transient antiphospholipid antibodies induced by acute Epstein-Barr virus infection

Splenic infarction is a rare feature of infectious mononucleosis (IM) due to Epstein-Barr virus (EBV), limited to three case reports. We report the first case of splenic infarction during acute EBV infection associated with the transient induction of antiphospholipid antibodies. We discuss the role of antiphospholipid antibodies in thrombosis in acute viral infections and postulate other mechanisms of thrombosis. Once other more common causes of splenic infarction, such as endocarditis and lymphoma, have been excluded, the possibility of viral-induced antiphospholipid antibodies should be considered.