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Biomedical subjects

G F Lucas

Publications and source records attributed to G F Lucas.

At least 19 recordsLinked to original sources
PubMed2005

Reactivity of T cells from women with antibodies to the human platelet antigen (HPA)-1a to peptides encompassing the HPA-1 polymorphism.

The human platelet antigen-1a (HPA-1a) is the most common alloantigenic target in fetal and neonatal alloimmune thrombocytopenia (NAIT). Treatment currently depends on the outcome in previous pregnancies. HPA-1 specific T cell responses were determined in 14 HPA-1a alloimmunized women during or after pregnancies affected by NAIT. Peripheral blood mononuclear cells were incubated with peptides encompassing the Leu33Pro polymorphism (residues 20-39 and 24-45 in both Leu33 (HPA-1a) and Pro33 (HPA-1b) forms) or control recall antigens in the presence of autologous sera and T cell proliferation was measured by (3)H-thymidine incorporation. Control antenatal and postpartum sera suppressed T cell proliferation and use of such sera was avoided. Most patients (86%) responded to the HPA-1a peptides with 64% also having weaker T cell proliferation to the HPA-1b peptides; 14% had no activity towards any peptide despite responding to control antigens. Administration of IVIG during pregnancy appeared to reduce T cell reactivity to HPA-1 peptides. Postnatal anti-HPA-1a T cell responses from women who had a severe history of NAIT (an intracranial haemorrhage in a previous fetus) were greater than those from women with a mild history. This assay may have the potential to predict disease severity if performed prior to or early in pregnancy.

Antigens, Human Platelet↗
PubMed2001

Immune neutropenia associated with anti-human neutrophil antigen-2a (NB1) antibodies following unrelated donor stem cell transplantation for chronic myeloid leukaemia: perpetuation by granulocyte colony-stimulating factor.

A case of immune neutropenia following unrelated stem cell transplantation for chronic myeloid leukaemia is described. The neutropenia developed following herpes zoster viral infection and was associated with antibodies to the human neutrophil antigen (HNA)-2a (formerly known as NB1). The neutropenia was prolonged, profound and unresponsive to granulocyte colony-stimulating factor (GCSF). The neutrophil count recovered after GCSF was discontinued. HNA-2a has been reported to be upregulated following GCSF administration. In the present case, it appears that the immune neutropenia may have been perpetuated by GCSF administration.

Adult↗
PubMed2001

Case report: four donors with granulocyte-specific or HLA class I antibodies implicated in a case of transfusion-related acute lung injury (TRALI).

A 54-year-old female patient with a history of chronic liver disease and portal hypertension was admitted for an elective cholecystectomy. Preoperative evaluation revealed a prolonged prothrombin time of 17.4 seconds (control 12 to 15.5 seconds). Six units of fresh frozen plasma (FFP) were prescribed after failure of correction of the coagulopathy with intravenous vitamin K (10 mgs). During infusion of the fifth unit of FFP, the patient became acutely dyspneic. Arterial blood gas analysis revealed marked hypoxemia (PO(2) 6.58 kPa) and the chest X-ray showed new diffuse bilateral alveolar infiltrates. The patient remained hypoxemic with unstable oxygen saturations over the following 7 days, during which time she required 60 to 100 percent oxygen administered by face mask. Intravenous methylprednisolone (200 mgs) was given for 5 days. Mechanical ventilation was not required. The lung infiltrates gradually cleared over 3 to 4 days and the patient showed clinical improvement after 1 week. Four of the donors of the implicated units of plasma were female and all had a history of pregnancy. Two donors had HLA class I antibodies and two had granulocyte-specific antibodies detectable in their serum. In crossmatch studies, granulocyte-reactive antibodies from two donors bound to granulocytes from the patient, which suggested that these antibodies were clinically relevant. These clinical and serologic findings support a diagnosis of transfusion-related acute lung injury (TRALI).

Journal Article↗
PubMed1999

Evaluation of an enzyme-linked immunosorbent assay kit (GTI PakPlus) for the detection of antibodies against human platelet antigens.

Twenty-six serum samples from 24 patients were investigated for the presence of platelet-specific antibodies in a partly retrospective (n = 15) and partly prospective (n = 9) study. The sera contained either alloantibodies to human platelet antigens (HPA) (n = 23) or were from clinically suspected cases of fetomaternal alloimmune thrombocytopenia (FMAITP) in which platelet-specific antibodies had not been detected (n = 3). Three techniques were used to detect platelet antibodies: the platelet immunofluorescence test, the monoclonal antibody immobilization of platelet antigens (MAIPA) assay and a commercially available enzyme-linked immunosorbent assay--GTI PakPlus (GTI kit). Two alkaline phosphatase-conjugated antiglobulin reagents provided by the manufacturer were used in the GTI kit: an antihuman IgG/IgA/IgM (IgGAM) conjugate and an antihuman IgG conjugate. The GTI kit with the anti-IgGAM conjugate failed to detect eight antibody specificities in seven sera (anti-HPA-1a [n = 3], anti-HPA-3a [n = 1], anti-HPA-3b [n = 1] and anti-HPA-5b [n = 3]). Greater signal-to-background ratios were achieved in the GTI kit with the anti-IgG conjugate but five antibody specificities (anti-HPA-1a [n = 1], anti-HPA-3a [n = 1], anti-HPA-3b [n = 1], anti-HPA-5b [n = 2]) remained undetectable. All the sera were detected by MAIPA assay and, furthermore, the MAIPA assay achieved the greatest signal-to-background ratio in the majority of sera tested. These findings re-emphasize the value of the MAIPA assay in reference laboratories and illustrate that the GTI kit may either fail to detect or incorrectly identify clinically significant HPA antibodies.

Antigens, Human Platelet↗
PubMed1997

Post-transfusion purpura (PTP) associated with anti-HPA-1a, anti-HPA-2b and anti-HPA-3a antibodies.

The serum from an 85-year-old man with a clinical diagnosis of post-transfusion purpura (PTP) was investigated for the presence of platelet-specific antibodies. Clinically, the case was typical of PTP but, unusually, the serum was found to contain multiple platelet-specific alloantibodies. Anti-HPA-1a, anti-HPA-2b and anti-HPA-3a antibodies were detected together with multispecific anti-HLA (class I) antibodies. Additional (but weaker) antibody reactivity was also observed with platelet glycoproteins (Gp) IIb/IIIa, GpIb and GpIa/IIa which lacked the antigens recognized by the alloantibodies, suggesting the presence of auto- or cross-reacting antibodies. The patient's genotype was HPA-1b/1b, HPA-2a/2a, HPA-3b/3b, HPA-5a/5b and was consistent with the platelet alloantibodies detected. The patient made a complete recovery following treatment with intravenous gamma-globulin.

Aged↗
PubMed1995

Predicting the severity of haemolytic disease of the newborn: an assessment of the clinical usefulness of the chemiluminescence test.

The ability of the chemiluminescence test (CLT) to predict the severity of haemolytic disease of the newborn (HDN) was determined in 80 alloimmunized pregnant women who delivered antigen-positive babies. In 54 cases of alloimmunization to D, results from the CLT showed better correlation with fetal outcome than anti-D concentration measured by AutoAnalyzer (r = 0.70 and 0.36 respectively). Results from the CLT permitted a threshold level of antibody activity (30%) below which 15/20 babies were unaffected or had mild disease, and only one required transfusion therapy in utero. CLT results above 30% were associated with moderate or severe disease in all cases. Results from the AutoAnalyzer proved a less reliable predictor of disease severity; three women with anti-D levels > 20 iu/ml delivered unaffected babies, and two women with anti-D levels < 10 iu/ml delivered babies who had required transfusion in utero. The clinical usefulness of the CLT derives from the possibility of avoiding invasive monitoring procedures in women with high levels of anti-D which is relatively non-functional.

Erythroblastosis, Fetal↗
PubMed1994

Prospective evaluation of the chemiluminescence test for the detection of granulocyte antibodies: comparison with the granulocyte immunofluorescence test.

A series of 213 neutropenic patients were tested for the presence of granulocyte antibodies using the granulocyte chemiluminescence test (GCLT) and the granulocyte immunofluorescence test (GIFT). Sera containing lymphocyte (HLA) antibodies were excluded from the study. A direct GIFT was performed on granulocytes from 56 patients. Samples were obtained from patients with a range of clinical conditions including primary adult autoimmune neutropenia, autoimmune neutropenia of infancy, autoimmune neutropenia secondary to Felty's syndrome, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, proliferative disorders, bone marrow transplantation and patients with documented febrile or pulmonary transfusion reactions. Overall, granulocyte antibodies were detected in 52.1% of patient sera. Results for the GCLT and GIFT (IgG) were strongly correlated (p < 0.001) for both primary and secondary immune neutropenias. The results confirm the applicability of the GCLT in the granulocyte serology laboratory.

Adult↗
PubMed1993

Predicting hemolytic disease of the newborn: a comparison of the monocyte monolayer assay and the chemiluminescence test.

The ability of the monocyte monolayer assay (MMA) and the chemiluminescence test (CLT) to predict the clinical significance of alloantibodies associated with hemolytic disease of the newborn (HDN) was assessed by the use of 22 well-characterized antisera--predominantly anti-D--from alloimmunized pregnant women. Seventeen sera were obtained before delivery from women whose infants were antigen positive for the antibody specificities identified in the maternal serum. With testing of these 17 sera by MMA, 10 results were in agreement with the presence or absence of HDN, but there were 5 false-positive and 2 false-negative results. With the CLT, 16 results were in agreement with the presence or absence of HDN, and there was 1 false-negative result. Five sera were obtained from women whose infants were antigen negative for the antibody specificities identified in the maternal serum. The CLT and the MMA were both subject to false-positive results with these sera. These results suggest that the CLT may be more valuable than the MMA as a noninvasive test for predicting the clinical significance of alloantibodies in HDN.

Erythroblastosis, Fetal↗
PubMed1992

The use of interferon-gamma-treated U937 cells in chemiluminescence assays to detect red cell, platelet and granulocyte antibodies of potential clinical significance.

The chemiluminescent (CL) response of interferon-gamma-treated U937 (IFN-U937) cells to sensitized target cells has been used to detect red cell, platelet and granulocyte antibodies. A clone of U937 cells was selected which expressed Fc receptor I (Fc gamma RI) and which, after incubation with IFN-gamma for 72 h, was capable of generating high levels of lucigenin-enhanced CL. The CL responses of IFN-U937 cells and peripheral blood human monocytes to sensitized red cells, platelets or granulocytes were then compared. Assays using monocytes or IFN-U937 cells were of comparable sensitivity for detection of antibodies against all three types of target cell. In addition, the use of IFN-U937 cells reduced interassay variation and simplified assay performance. The potential clinical usefulness of these CL assays was suggested by the ability of both monocytes and IFN-U937 cells to respond to red cells, platelets or granulocytes sensitized with sera from pregnant women whose babies had either haemolytic disease of the newborn (HDN), alloimmune thrombocytopenia or alloimmune neutropenia respectively. In addition, monocytes and IFN-U937 cells both responded to red cells sensitized with antibodies against a variety of specificities of assumed (although not documented) clinical significance for blood transfusion recipients. In contrast, monocytes and IFN-U937 cells responded only weakly to red cells sensitized with either anti-D in sera from mothers of babies unaffected by HDN, or with antisera containing high titre antibodies with specificities not normally associated with significantly reduced red cell survival.

Acridines↗
PubMed1992

Autoimmune neutropenia of infancy.

AIM: Assessment of the clinical and haematological course of autoimmune neutropenia of infancy (ANI) in a defined childhood population in the south east of Scotland. METHODS: From January 1986 to February 1991 all children presenting with persistent neutropenia were examined serologically for evidence of antigranulocyte antibodies. The clinical course of those children found to have anti-granulocyte antibodies was then closely monitored. RESULTS: During the study period five children had serologically confirmed ANI, giving an annual incidence of approximately 1/100,000 in this population. All of these cases followed the classic benign course of the condition. The presenting illnesses were mild, often with superficial skin sepsis and the initial absolute neutrophil count (ANC) ranged from 0.00-0.87 x 10(9)/l. All have remained well with no serious infections. Two children attained a normal ANC after 14 and 24 months respectively, the others currently remain neutropenic. CONCLUSIONS: Autoimmune neutropenia of infancy is a condition which rests on a serological diagnosis. It follows a chronic benign course and all children eventually attain a normal ANC. The level of antigranulocyte antibody in the serum often begins to wane prior to improvement in the ANC and can give an indication of when recovery will begin to occur.

Autoantibodies↗
PubMed1991

Late onset immune pancytopenia following bone marrow transplantation.

A 17-year-old boy developed autoimmune pancytopenia in the absence of chronic graft-versus-host disease 170 d after allogeneic bone marrow transplantation (BMT) from his HLA identical brother. The anaemia and thrombocytopenia responded to conventional immunosuppressive treatment, but the neutropenia was refractory to this and to splenectomy and subsequent removal of splenic remnant. Following total lymphoid irradiation the neutrophil count rose to low normal levels but thrombocytopenia and anaemia secondary to marrow hypoplasia required transfusion support. Bone marrow function was finally normalized by an additional transfusion of donor marrow without prior immunosuppressive therapy. We conclude that late onset immune pancytopenia post BMT caused by antibodies of probable donor origin may be life threatening in the absence of chronic graft-versus-host disease.

Adolescent↗
PubMed1991

Clinical evaluation of the effects of storage time and irradiation on transfused platelets.

Platelet concentrates stored for up to 5 days at room temperature or irradiated with 15 Gy immediately prior to transfusion were evaluated for their ability to increase the platelet count in thrombocytopenic patients. Platelets irradiated with a dose of 15 Gy immediately prior to transfusion achieved corrected increments (CI) at 1 and 20 h after transfusion no different from those achieved by non-irradiated platelets. Storage for 5 days reduced the mean 1-hour CI to 5.7 compared with a mean of 12.3 achieved by platelets transfused after only 1-day storage (p = 0.008). Similarly, the frequency of a repeat transfusion being indicated within 24 h increased with increasing storage time (p = 0.005).

Blood Platelets↗
PubMed1990

Transfusion of ABO-mismatched platelets leads to early platelet refractoriness.

Forty-three consecutive patients previously unexposed to platelets and undergoing treatment for acute leukaemia or autografting for relapsed Hodgkin's lymphoma were randomized to receive transfused platelets of either their own ABO group (OG) or of a major mismatched group (MMG). The 26 evaluable patients were equally distributed between the two study groups. Nine of 13 (69%) MMG patients became refractory with a median onset at transfusion 7 (15 d), compared with only one of 13 (8%) OG patients (P = 0.001). Refractoriness was associated with the formation of high titre isoagglutinins, anti-HLA and platelet specific antibodies. In one patient refractoriness appeared to be due to high titre isoagglutinins alone. Six other patients developed an increase in isoagglutinin titre sufficient to adversely affect platelet increments. Patients receiving ABO-mismatched platelets had a higher incidence of anti-HLA antibodies (5 v. 1) and platelet specific antibodies (4 v. 1). ABO-mismatched platelets transfused prior to the onset of refractoriness resulted in increments similar to those achieved by ABO-matched platelets. The study demonstrates that ABO-mismatched platelets are as effective as matched platelets in patients with low titre isoagglutinins requiring only few transfusions. However, the greater incidence of early refractoriness induced in MMG patients indicates that ABO-mismatched platelets should not be given to patients with marrow failure requiring long-term support.

ABO Blood-Group System↗