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CD31 mismatching and GvHD
Biomed
& Phnrmacorher
1996;50:320-321 0 Elsevier, Park
Notes
CD31
mismatching
and GvHD
Graft versus host disease (GvHD) is a frequent and often fatal complication of allogeneic bone marrow transplantation (BMT). Because nearly all BMT donors are major histocompatibility (HLA) matched to their recipients, most GvHD in man is caused by incompatibilities of minor (ie, non-HLA) transplantation antigens. Human minor histocompatibility antigens are, however, poorly defined. We postulated that such antigens would be present at sides of early contact between transplanted tissue and its host. The CD31 adhesion molecule therefore seemed a likely candidate alloantigen because of its constitutive expression on vascular endothelial cells and its possible polymorphism based on limited sequence data. Relevant exons of CD31 cDNA from 21 unrelated donors were directly sequenced. A single polymorphism was observed involving a Leu-Val substitution at codon 125, with each allele having a gene frequency of approximately of 0.5. HLA identical sibling BMT patients from the extreme ends of the spectrum of GvHD were identified; 32 with no GvHD and 14 with severe, acute GvHD. Patients and their donors were CD31 typed using PCR with specific primers for each allele. CD31 identity with their donors was observed in 78% of patients with no GvHD, but in only 29% of patients with severe, acute GvHD (P = 0.004). Additional evidence of immunoreactive differences between CD3 1 alleles was shown by their differential reactivity with selected antiCD3 1 monoclonal antibodies. These data demonstrate that CD31 is polymorphic, and that mismatching for CD3 1 alleles is associated with increased risk of severe, acute GvHD. Prospective CD31 typing is readily feasible and may reduce that risk. Stanford
(1) N Engl
J Med
University
Blood
thing). Unfortunately, patients with long-standing insulin-dependent diabetes (IDDM) frequently report reduced ability to recognise the onset of hypoglycaemia and thus are at risk of severe neuroglycopaenia. Hypoglycaemia unawareness may in turn, be associated with defective glucose counterregulation, in particular, a defective adrenaline response to a falling blood glucose level. Caffeine, a widely available constituent of coffee, tea, soft drinks, confectionaries and over-the-counter remedies for colds and flu, simultaneously decreases cerebral blood flow and increases use of cerebral glucose. Thus, caffeine may theoretically induce neuroglycopaenia if the supply of substrate to the brain is compromised by a decrease in peripheral glucose levels. Under laboratory conditions, we found that prior ingestion of 250 mg (equivalent to two or three cups of coffee) caused a reduction in cerebral blood flow associated with greater awareness compared to an identical placebo study, when blood glucose levels were lowered into the frankly hypotlycaemic range (2.8 mmol/L). The hormonal counterregulatory response (particularly adrenaline) was also augmented by prior caffeine ingestion whereas cognitive function (P300 auditory evoked responses) was unaffected. Although, theoretically, the effects of caffeine on glucose counterregulatory hormone levels might limit the ability of diabetic patients to attain euglycaemia, caffeine could be beneficial by helping to improve the ability of patients with IDDM to detect the onset of hypoglycaemia without adverse effects on cognitive function. The
(2) Lance?
Royal Bournemouth Bournemouth BH7
D Kerr (2) Hospital, 7DW, UK
1996;347:19-24
C Grumet (1) Center, Palo Alto, CA 94304, USA
1996;334:266-91
Caffeine and the perception of hypoglycaemia The best defence against hypoglycaemia is the ability to recognise it and take appropriate action (ie, eat some-
Structure of HCV-lb and the response to interferon therapy We found a region that was associated with the resistance to interferon in the nonstructural protein 5A (NSSA) region of hepatitis C virus (HCV) genotype-lb. Then, we investigated whether or not the response to interferon could be predicted before interferon therapy
& Phnrmacorher
1996;50:320-321 0 Elsevier, Park
Notes
CD31
mismatching
and GvHD
Graft versus host disease (GvHD) is a frequent and often fatal complication of allogeneic bone marrow transplantation (BMT). Because nearly all BMT donors are major histocompatibility (HLA) matched to their recipients, most GvHD in man is caused by incompatibilities of minor (ie, non-HLA) transplantation antigens. Human minor histocompatibility antigens are, however, poorly defined. We postulated that such antigens would be present at sides of early contact between transplanted tissue and its host. The CD31 adhesion molecule therefore seemed a likely candidate alloantigen because of its constitutive expression on vascular endothelial cells and its possible polymorphism based on limited sequence data. Relevant exons of CD31 cDNA from 21 unrelated donors were directly sequenced. A single polymorphism was observed involving a Leu-Val substitution at codon 125, with each allele having a gene frequency of approximately of 0.5. HLA identical sibling BMT patients from the extreme ends of the spectrum of GvHD were identified; 32 with no GvHD and 14 with severe, acute GvHD. Patients and their donors were CD31 typed using PCR with specific primers for each allele. CD31 identity with their donors was observed in 78% of patients with no GvHD, but in only 29% of patients with severe, acute GvHD (P = 0.004). Additional evidence of immunoreactive differences between CD3 1 alleles was shown by their differential reactivity with selected antiCD3 1 monoclonal antibodies. These data demonstrate that CD31 is polymorphic, and that mismatching for CD3 1 alleles is associated with increased risk of severe, acute GvHD. Prospective CD31 typing is readily feasible and may reduce that risk. Stanford
(1) N Engl
J Med
University
Blood
thing). Unfortunately, patients with long-standing insulin-dependent diabetes (IDDM) frequently report reduced ability to recognise the onset of hypoglycaemia and thus are at risk of severe neuroglycopaenia. Hypoglycaemia unawareness may in turn, be associated with defective glucose counterregulation, in particular, a defective adrenaline response to a falling blood glucose level. Caffeine, a widely available constituent of coffee, tea, soft drinks, confectionaries and over-the-counter remedies for colds and flu, simultaneously decreases cerebral blood flow and increases use of cerebral glucose. Thus, caffeine may theoretically induce neuroglycopaenia if the supply of substrate to the brain is compromised by a decrease in peripheral glucose levels. Under laboratory conditions, we found that prior ingestion of 250 mg (equivalent to two or three cups of coffee) caused a reduction in cerebral blood flow associated with greater awareness compared to an identical placebo study, when blood glucose levels were lowered into the frankly hypotlycaemic range (2.8 mmol/L). The hormonal counterregulatory response (particularly adrenaline) was also augmented by prior caffeine ingestion whereas cognitive function (P300 auditory evoked responses) was unaffected. Although, theoretically, the effects of caffeine on glucose counterregulatory hormone levels might limit the ability of diabetic patients to attain euglycaemia, caffeine could be beneficial by helping to improve the ability of patients with IDDM to detect the onset of hypoglycaemia without adverse effects on cognitive function. The
(2) Lance?
Royal Bournemouth Bournemouth BH7
D Kerr (2) Hospital, 7DW, UK
1996;347:19-24
C Grumet (1) Center, Palo Alto, CA 94304, USA
1996;334:266-91
Caffeine and the perception of hypoglycaemia The best defence against hypoglycaemia is the ability to recognise it and take appropriate action (ie, eat some-
Structure of HCV-lb and the response to interferon therapy We found a region that was associated with the resistance to interferon in the nonstructural protein 5A (NSSA) region of hepatitis C virus (HCV) genotype-lb. Then, we investigated whether or not the response to interferon could be predicted before interferon therapy