Search PubMed⌕ Search

Biomedical subjects

S D Litwin

Publications and source records attributed to S D Litwin.

At least 19 recordsLinked to original sources
PubMed1990

Selective concentration of IgD class-specific antibodies in human milk.

The participation of human IgD class antibody in local immune responses of breast tissue was studied by analysing the sera-to-milk ratios of total IgD, IgM, IgA, IgG isotypes and albumin found in matched samples, and by analysing the sera-to-milk (S/M) ratios of IgD, IgM, IgA, IgG antibodies against Haemophilus influenzae capsular polysaccharide (PRP), phosphorylcholine, tetanus and in some cases diphtheria antigens. The study group consisted of eight women immunized during pregnancy with PRP, and control, unimmunized women. Albumin, and total IgG showed high S/M ratios. IgA had a low S/M ratio as expected, consistent with reports that IgA is locally concentrated. Total IgD and IgM isotype ratio values were intermediate between IgG and IgA suggesting they were selectively concentrated in breast fluids due to local production or transport mechanisms, or both. Ratios for specific antibodies of IgA and IgM isotypes and for total IgA and IgM isotype showed parallel data. Among the IgD antibodies, those specific for PRP and phosphorylcholine suggested a higher degree of selective concentration as compared with tetanus antigen. In the group of unimmunized women, although selective concentration of total IgD was observed, specific antibody studies were inconclusive due to the low milk IgD antibody levels encountered. The results indicate that IgD (and also IgM) may participate in local immune responses of human breast tissues and fluids; possibly influenced by the nature of the antigen, the state of immunization and the hormonal environment (pregnancy).

Enzyme-Linked Immunosorbent Assay↗
PubMed1988

In vitro studies on human IgD. III. Immunologic features of individuals with high sera IgD and spontaneous IgD biosynthesis.

The immunologic characteristics of normal persons with high sera IgD values were analyzed. Elevated sera IgD appeared to be the consequence of increased biosynthesis as reflected by an increased number of IgD-Ig-containing cells, an elevated sera IgD, lambda/kappa ratio, and increased spontaneous IgD secretion in vitro. These same findings have been previously linked to increased IgD production (S.D. Litwin and B.D. Zehr, Eur. J. Immunol. 17, 483, 491, 1987). Elevated sera IgD proved relatively stable over 21 months, in five selected individuals, favoring a genetic vs acquired explanation. The failure of sera IgG, IgA, and IgM to positively correlate with IgD weighed against polyclonal Ig synthesis. However, high IgD was inversely correlated to IgM class values and a high sera IgD subset of the population (greater than 31 micrograms/ml) had lower levels of certain IgM antibodies. Analysis of spontaneous IgD secretion, an event frequently encountered in high sera IgD persons, discloses 2/29 cultures with rising supernatant IgD implying in vitro induction. The results emphasize a role for active IgD biosynthesis in the immune responses of certain individuals.

Cells, Cultured↗
PubMed1987

In vitro studies on human IgD. I. Sources and characteristics of "externalized" IgD in tonsil lymphocyte cultures.

As part of a broader analysis into the function of IgD, and especially into the role of human IgD-secreting cells, fresh human tonsil lymphocyte cultures were analyzed. The goals were to define the origins of "externalized" supernatant IgD and to examine its relationship to spontaneous Ig secretion of IgG, IgM and IgA. Assayable IgD was found by 24 h in cultures without added mitogens. "Externalized" IgD comprised a small fraction (1.6-1.8%) of supernatant Ig when compared to the fraction of IgD-containing cells (congruent to 10%): IgD appears to disappear rapidly in vitro. Initial experiments employing irradiation and chemical inhibitors of protein synthesis suggested that "externalized" IgD was produced de novo during culture rather than representing preformed or cytophilic Ig. Most significantly, tonsil cultures with higher IgD values (greater than 20 ng IgD/10(6) cells, day 7) showed convincing evidence that secreted IgD was a major source for "externalized" IgD. This evidence included the amount of "externalized" IgD depended on viable culture conditions; radioincorporated 35S appeared as a visible IgD band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels; "higher" IgD cultures showed increased numbers of IgD-Ig-containing plasma cells, and IgD, lambda in excess of IgD, kappa; both events are associated with IgD secretion. In cultures producing high amounts of IgD, IgD secretion appeared to be spontaneous rather than induced and was independent of the polyclonal spontaneous Ig secretion of other Ig isotypes. Low titers of inhibitable IgD isotype anti-phosphorylcholine antibodies but not IgD isotype anti-polyribotol phosphate antibodies were present in tonsil supernatants: both were present in matched sera. Other laboratories have directed attention to the striking and possibly selective participation of human tonsil lymphocytes in IgD synthesis using other approaches. Present results supplement and expand earlier data and support the practical value of analysis of short-term cultured tonsil lymphocytes. Differentiation to IgD-secreting cells is suggested to be an active, underestimated and putatively an important part of the immune response in the human tonsil.

Antibodies, Anti-Idiotypic↗
PubMed1987

In vitro studies on human IgD. II. IgD-secreting cells preferentially elaborate IgD, lambda molecules.

The "IgD paradox" describes the unexpected finding that, despite a predominance of kappa (kappa) light (L) chains on the surface of IgD+ human B cells, the majority of monoclonal IgD proteins are of lambda (lambda) type. This potentially informative phenomenon appears to be based on a preferential association between delta (delta) heavy (H) and lambda L chains of IgD-secreting cells. The current studies analyze the phenomenon in vitro. Initial assays on tonsil "spent" supernatants showed that the higher IgD-"externalizing" cultures displayed progressively elevated IgD, lambda/kappa ratios due to parallel shifts in total IgD and IgD, lambda while IgD, kappa remained stable. The cells of the same higher-IgD cultures demonstrated that individual IgD-containing cells had a predominance of lambda chains in contrast to IgM-containing cells of the same cultures using fluorochrome-antibody double staining. Certain tonsil culture IgD-containing cells remarkably appeared to have exclusively lambda chain. These same tonsils show evidence of IgD secretion (Litwin, S. D. and Zehr, B. D., Eur. J. Immunol. 1987. 17:483); thus, these data align preferential delta-lambda chain association with IgD-secreting normal tonsil B cells in vitro and emphasize the usefulness of IgD, lambda/kappa ratio in monitoring IgD secretion. In another approach the relationship between the cellular location of IgD and the preferential delta-lambda chain association was studied using Triton X-114-partitioned cell lysates. IgD, lambda/kappa ratios were one or less in the detergent phase (membrane-enriched fraction) consistent with expected IgD, kappa predominance in membrane IgD. In contrast, the aqueous phase (intracellular-enriched fraction) of IgD-secreting cultures had 2-4 times higher supernatant IgD, lambda/kappa ratios. The restriction of high IgD, lambda/kappa ratios to intracellular fractions and supernatants of IgD-secreting cultured cells parallels the predicted distribution of secretory IgD. In sera studies, the correlation between total IgD and IgD, lambda/kappa ratio values was consistent with secreted sera IgD showing preferential lambda chain expression. It was concluded that the phenomenon of delta-lambda chain preferential association is expressed in vitro as well as in vivo; a property of normal, nonmalignant human IgD-secreting B cells; and closely related to the secretory form of IgD. In certain cultures, the delta-lambda chain preference was so striking as to imply limited heterogeneity of the IgD immune response.

Antigens, Surface↗
PubMed1987

Membrane IgD-positive B cells of "low-IgD serum phenotype" individuals fail to secrete IgD and fail to shift to preferential lambda light-chain expression in vitro.

IgD production by short-term human peripheral blood mononuclear cell (PBM) cultures was studied to establish the in vitro correlates of low serum IgD expression. Cells of persons with less than 3 micrograms/ml IgD in the serum, referred to as the low-serum IgD phenotype (LISP), were analyzed. Advantage was taken of recently developed data on spontaneous IgD biosynthesis by human B cells and the observation that lambda light chains are preferentially expressed by IgD-secreting cells in vitro. Initial analysis of an IgD serum distribution showed that all LISP sera contained low but detectable amounts of IgD, with a mean value of 0.85 microgram/ml; this figure was 30- to 35-fold lower than the mean of the majority of the population. LISP PBM contained normal numbers of IgD-positive B cells which displayed a normal intensity of IgD per cell using comparative analysis of mean channel fluorescence by cell flow cytometry. Several lines of evidence suggested that IgD-secreting cells could not be generated from LISP lymphocytes in vitro. Namely, it was found that no IgD immunoglobulin-containing cells were found among PBM of LISP persons; cell lysates enriched for the intracellular fraction by Triton X-114 phase separation showed low IgD in LISP cells despite "normal" amounts of IgD in membrane-enriched fraction preparations; there was no spontaneous IgD secretion by any LISP PBM cultures; and neither LISP sera nor cellular IgD preparations showed IgD lambda/kappa ratios greater than 1.0, indicative of the absence of the preferential lambda light-chain expression associated with secretion of IgD.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗
PubMed1987

Human IgD and IgA1 compete for D-galactose-related binding sites on the lectin jacalin.

Lectin selectivity for human Ig classes is based on carbohydrate differences. Earlier reports that the lectin jacalin precipitated human IgA were confirmed and supplemented by the current study, which demonstrates that jacalin also binds human IgD as evaluated by micro-ELISA and SDS-PAGE. Experimental findings indicated that: (i) Monoclonal and polyclonal (sera) IgD, IgA1, but not IgA2, IgM, or IgG1-4 reacted with jacalin. (ii) Six tested monoclonal IgD proteins each bound approximately equally to jacalin when antigenicity rather than protein concentration was measured: the results weigh against the presence of jacalin-detectable IgD subclasses or genetic variants. (iii) IgD and IgA1 both associated maximally in 4-8 h at 4 degrees C. There was no dissociation at 4 degrees C but limited dissociation occurred at 37 degrees C after 24 h. (iv) Both IgD and IgA1 were eluted from jacalin by galactose-related sugars. (v) IgD and IgA1 bind competitively to jacalin. The results suggested that jacalin reacts with O-linked oligosaccharide N-acetyl-galactosamine (GalN) residues found on the hinge region of both IgD and IgA1. Jacalin also interacted with one major and several minor unidentified sera proteins. The findings offer an approach to the isolation of serum polyclonal IgD and to the characterization of the unusual carbohydrates of the human delta heavy chain with respect to their function.

Antibodies, Monoclonal↗
PubMed1986

Relation between clinical features of the mitral prolapse syndrome and echocardiographically documented mitral valve prolapse.

Mitral valve prolapse, the most common inherited cardiovascular condition, has been associated with a variety of signs, symptoms and electrocardiographic abnormalities, but the true spectrum of the mitral prolapse syndrome remains in doubt because clinical findings often contribute to patient identification and their prevalence in patient groups may be overstated because of ascertainment bias. Accordingly, clinical findings in 88 patients with echocardiographic mitral prolapse were compared with those in 81 of their adult first degree relatives with mitral prolapse (a group free of ascertainment bias) and in two control groups without mitral prolapse: 172 first degree relatives and 60 spouses. Comparison of relatives with and without mitral prolapse demonstrated true associations between mitral prolapse and clicks or murmurs, or both (67 versus 9%, p less than 0.001), thoracic bony abnormalities (41 versus 16%, p less than 0.001), systolic blood pressure less than 120 mm Hg (53 versus 31%, p less than 0.001), body weight 90% or less of ideal (31 versus 14%, p less than 0.005) and palpitation (40 versus 24%, p less than 0.01). In contrast, relatives with mitral prolapse showed no significant increase over normal relatives or spouses without mitral prolapse in prevalence of chest pain, dyspnea, panic attacks, high anxiety or repolarization abnormalities, but these features were all more common in women than in men (p less than 0.01 to less than 0.001). Thus, the true spectrum of the mitral prolapse syndrome encompasses a midsystolic click and late systolic murmur, thoracic bony abnormalities, low body weight and blood pressure and palpitation. Other suggested clinical features, including nonanginal chest pain, dyspnea, panic attacks and electrocardiographic abnormalities, have appeared to be associated with mitral valve prolapse because of ascertainment bias and an erroneous classification of differences between men and women as being due to mitral valve prolapse.

Adolescent↗
PubMed1985

Studies on human low serum IgD phenotype and Gm markers.

The human "low serum IgD phenotype" was studied by simultaneous Gm typing and IgD immunoassay of several populations. An association between Gm (f+b+) haplotype and low human IgD was confirmed and extended to the "low serum IgD phenotype"--as defined from population distribution and genetic studies by Dunnette et al. 1978. Further, it was shown that Black American sera determined by Gm haplotype, had a similar percentage of "low serum IgD phenotype" samples (16%) although they lacked the "associated" Gm(f+b+) haplotype of White American samples. Sardinian sera showed a low incidence of the "low serum IgD phenotype" which was not correlated with Gm haplotype distribution. Familial aggregation of the "low serum IgD phenotype" was observed. No association was found between "low serum IgD phenotype" and serum IgE values. Age related abiotrophy of IgD could not be attributed to selective survival of "low serum IgD phenotype" persons.

Adult↗
PubMed1984

The effect of smoking during pregnancy on cord blood and maternal serum immunoglobulin levels.

The effect of smoking on the fetal and maternal humoral immune parameters was evaluated in cord and maternal blood, collected at delivery from 163 mothers who smoked and 130 mothers who did not smoke, and their offspring. There was no difference in time of gestation between the two groups, but the mean birth weight of the offspring of mothers who smoked was decreased, as previously observed. There were higher levels of IgA (p less than 0.01), IgM (p less than 0.001), and IgG (p less than 0.001) in cord sera of children of mothers who smoked than in the offspring of mothers who did not smoke. Mothers themselves who smoked had higher levels of IgM (p less than 0.001) and IgG (p less than 0.001), but not IgA, as compared to control mothers who did not smoke. Since cord IgA and IgM are produced by the fetus, these results could be interpreted as being due to either a higher incidence of infection in utero or metabolic differences in the children of mothers who smoke. Either of these possibilities may explain the increased frequency of postpartum endometritis, increased incidence of fetal distress, and the characteristic of meconium-stained amniotic fluid in mothers who smoke.

Adult↗
PubMed1984

Correlation between maternal and fetal immunoglobulin E levels.

Immunoglobulin E (IgE) concentrations were measured in 157 paired samples of maternal-fetal sera. A correlation was found between maternal and fetal IgE levels, in contrast to earlier reports dealing with smaller series. The correlation is probably not due to placental transfer of maternal IgE but rather to genetic factors. The possible role of IgE in the fetal immune response is discussed.

Female↗
PubMed1983

The fetal serum alpha-fetoprotein and its relationship to immunoglobulins and birth weight at term.

The distribution of values of alpha-fetoprotein (AFP) was analyzed in the cord blood of 350 newborns divided into groups according to whether their mothers were normal, preeclamptic, or smokers. In addition, fetal birth weight and fetal IgA and IgM at term were correlated with AFP. Cord serum AFP values showed a unimodal bell-shaped distribution in 269 normal newborns with a mean of 22.7 +/- 11.3 (SD) micrograms/ml. The cord sera of infants of preeclamptic mothers and of smoking mothers showed a similar mean and distribution. As previously observed, AFP was correlated inversely with birth weight. No correlation existed between AFP and fetal Ig levels.

Birth Weight↗
PubMed1982

Does the X chromosome have a special role in immune biology?

The observation that a number of gene clusters or "supergenes" are critical in the genetic regulation of the immune response was used to introduce the hypothesis that multiple X chromosome genes are similarly organized and that they play some special critical role in the immune response. The evidence discussed included current information on several of the human X-linked immune deficiencies, data from mice and studies suggesting X chromosome genes have "regulatory" functions in non-immune tissues. A set of potentially testable speculations based on the hypothesis were advanced.

Animals↗
PubMed1981

Induction of immunoglobulin synthesis in corticosteroid-treated blood lymphocytes of a patient with acquired agammaglobulinemia.

Coculture experiments between lymphocytes of a 17-year-old immunodeficient male, DL, and a group of normal subjects, assaying pokeweed mitogen (PWM)-stimulated Ig secretion as a measure of B-cell function, revealed immunoregulatory abnormalities. Initial studies disclosed that DL had corticosteroid-sensitive T suppressor (Ts) cells capable of blocking Ig secretion by both HLA-identical and HLA-nonidentical cells in coculture. Cocultures of DL's peripheral blood mononuclear cells could be induced to secrete Ig in large amounts after certain maneuvers--the most informative of which involved mixing prednisolone-treated DL mononuclear cells with any normal T lymphocytes except those from DL himself. When these same experimental manipulations were performed individually, i.e., prednisolone treatment of cultured DL cells to remove Ts activity, or mixing equal numbers of normal T cells with untreated DL mononuclear cells, Ig was not produced. The data indicated that the T-cell abnormalities in DL included an excess of Ts cells and a deficiency to T helper (Th) cells. When repeat studies were performed later in the clinical course, during which interval a number of clinical interventions were attempted, it was found that the patient's cells were no longer corticosteroid sensitive and, further, they suppressed only HLA-identical cells.

Adolescent↗
PubMed1981

Decreased cord blood IgM and IgA in trisomy 21.

Disagreement as to whether Ig levels are high, low, or normal at different ages in different groups of trisomic children has interfered with defining the associated immunodeficiency state. Fetal Ig production was assessed by measuring cord blood IgM and IgA of five trisomy 21, 97 normal, and 37 control newborns with other birth defects. Trisomic infants showed significantly lower values. Cord blood IgG values showed no differences between groups when corrected for fetal blood weight. The data indicate that children with trisomy 21 have an impaired humoral immune response to utero.

Down Syndrome↗