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epitope on the same molecule (and residing on their common "cross-reacting" antigen), that is necessary to provide help to the B2 cells.Thus they rarely produce an IgG response to A/B antigens.However, under certain circumstances, usually involving
"hyperstimulation", group A and B individuals produce some IgGin response to the appropriate ABO blood group antigen, althoughIgM predominates. In most of the cases studied by Contrerasl largedoses of antigen were used in previously sensitised group A and Bindividuals, and an IgG response was seen. It is my contention thatthe source of these IgG antibodies was the B 1 (T-independent) Bcells. Had Contreras analysed the IgG subclass of the response itwould have been found to be of restricted isotype in subjects ofgroup A and B, the major isotype being IgG2. This is because in mancarbohydrate T-independent antigens elicit a clonally restrictedIgG2 response by direct "selection" ofBl cells, no T-cell switchingbeing involved. IgG2 is a very poor complement activator andcannot easily cross the placenta.Group 0 individuals can recognise the cross-reacting antigen
common to group A and B substance and provide T-help to A or Bspecific T-dependent B2 cells. Findings in Contreras’ study Isupport this hypothesis. When group 0 subjects were immunisedwith purified group A substance, they developed a significantincrease in IgM and IgG anti-B activity in addition to the expectedrise in anti-A. Similarly group 0 individuals produced a significantrise in anti-A in response to B substance. Contreras et al call this a
non-specific response, and offer no explanation. According to myhypothesis the injection of group A (or B) substance caused therecruitment of a large number of T-helper cells specific to epitopeson their common cross-reacting antigen. Some of these were thenable to provide help to any B2 cells specific to B (or A) present in asufficiently activated state to respond.The role of macrophages in B-cell responses to T-independent
and T-dependent antigens is well known; in the interests of brevityit was not discussed in my hypothesis as it had no direct bearingupon it.The hypothesis that only group 0 individuals are capable of
providing T-cell help to B2 cells during a response to T-dependentABO antigens predicts that they will be able to produce lessrestricted immune responses to such antigens than individuals ofgroup A or B. Thus they more readily produce IgG including IgGI 1and IgG3 with their greater destructive power.
It is only by careful in-vitro study that the hypothesis can beproven or dismissed and the necessary investigations are already inprogress.
Division of Pathology,Royal Infirmary,Sunderland SR2 7JE L. A. KAY
1. Contreras M, Armitage SE, Hewitt PE Response to immunisation with A and Bhuman glycoproteins for the procurement of blood grouping reagents Vox Sang1984; 47: 224-35.
2 Perlmutter RM, Hansburg D, Brides DE, Nicolotti RA, Davie JM. Subclass restrictionof anti carbohydrate antibodies. J Immunol 1978; 121: 566-72.
MATERNAL WEIGHT ADJUSTMENT AND LOWSERUM &agr;-FETOPROTEIN VALUES
SIR,-During the second trimester of pregnancy, serum a-feto-protein (AFP) levels have been found to depend, in part, onmaternal weight. 1,2 Johnson and Langley3 have recommended thata weight correction be incorporated routinely into the
interpretation of AFP test results. Adjustments such as this take onadded significance now that an association has been found betweenlow serum AFP levels and Down syndrome. 4,5 For weightadjustment, we divide the unadjusted multiple of median (MoM) bythe median value expected for that maternal weight, using theformula:
Expected median= 1 ’555—0-00190 (mateinal weight, in kg)or
Expected median = I -555-0-00417 (maternal weight, in Ib)The table summarises the effect of weight adjustment on the
percentage of women in our screening programme with AFP valuesbelow 0-5 5 MoM. Both the unadjusted and adjusted populationshave their median values set to 1 - 0 MoM. Analyses are restricted tofirst samples.
SERUM AFP VALUES BEI,OW 0 - 5 MOM BEFORE AND AFTER
ADJUSTMENT FOR MATERNAL WEIGHT
*1 kg=2.19 1b. _ _ . _ _ _._
Weight adjustment reduces the population below 0 - 5 MoM by12%, removing 218 of the women from the original populationunder 0 - 5 MoM but also adding 108 women who previously fellabove or equal to that level. For this adjustment to be beneficial, itwould be necessary to demonstrate that women with Down
syndrome pregnancies are randomly distributed according to
weight and that weight does not influence the rate or direction ofmisdating. Cuckle et al2 have reported that maternal weight doesnot explain the AFP association with Down syndrome, and we havefound no significant differences in gestational dating inaccuracies atthe various weight intervals (calculated from last menstrual periodand delivery dates).Using Hook’s estimates of Down syndrome incidence at the time
of amniocentesis for a 33-year-old population, the odds are 1:170 inthe 924 women selected with unadjusted MoM, while in those 801selected after weight adjustment, the overall odds are 1:150. Bothyield an estimated identification of just over 5 Down pregnancies.Thus, an increase in specificity is gained by maternal weightadjustment without loss in sensitivity.
Foundation for Blood Research,
Scarborough, Maine 04074, USA
G. E. PALOMAKIG. J. KNIGHTE. M. KLOZA
J. E. HADDOW
1. Haddow JE, Kloza EM, Knight GJ, Smith DE. Relationship between maternal weightand serum alpha-fetoprotein concentrations during the second trimester Clin Chem1981; 27: 133-34
2 Wald NJ, Cuckle HS, Boreham J, Terzian E, Redman C The effect of maternal weighton maternal serum alpha-fetoprotein levels. Br J Obstet Gynaecol 1981; 88:1094-96
3. Johnson AM, Langley L. Correction formula for maternal serum alpha-fetoproteinLancet 1984; ii: 812.
4 Merkatz IR, Nitowsky HM, Macri JN, Johnson WE. An association between lowmaternal serum alpha-fetoprotein (AFP) and fetal chromosome abnormalities. Am JObstet Gynecol 1984; 148: 886-91.
5. Cuckle HS, Wald JN, Lindenbaum RH Maternal serum alpha-fetoproteinmeasurement: A screening test for Downs syndrome Lancet 1984, i: 926-29.
6 Hook EB, Cross PK, Schreinemachers DM Chromosomal abnormality rates atamniocentisis and in live-born infants. JAMA 1983; 249: 2034-38.
NEW USE FOR IN-FLIGHT STETHOSCOPES
SIR,—DR Rubenstein and Mr Scott have both proposed (Feb 9,p 353) that airlines should carry a stethoscope for use in medicalemergencies. It is difficult, however, to know where to draw theline-if stethoscopes, why not comprehensive first-aid kits, andthence why not a selection of drugs to treat some of the morecommon emergencies? That argument aside, why do not moredoctors carry their own stethoscopes on flights? Apart fromallowing those who were keen to help any sufferers to be easilyidentified, I have found that, after detachment of the bell, the end ofthe tube can be inserted into the requisite hole to facilitate freelistening of the in-flight film, thus avoiding the extortionate chargesmade by the airlines for rental of head-sets. A word of warning,however; you need one of the longer stethoscopes, otherwise youhave to watch the film bent almost double.
Department of Surgery,Addenbrooke’s Hospital,Cambridge CB2 2QQ NICHOLAS I. MARKHAM