Citrullination facilitates cross-reactivity of rheumatoid factor with non-IgG1 Fc epitopes in rheumatoid arthritis.

Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are the two most prevalent autoantibodies in rheumatoid arthritis (RA), and are thought to have distinct autoantigen targets. Whilst RF targets the Fc region of antibodies, ACPAs target a far broader spectrum of citrullinated peptides. Here we demonstrate significant sequence and structural homology between proposed RF target epitopes in IgG1 Fc and the ACPA target fibrinogen. Two of the three homologous sequences were susceptible to citrullination, and this modification, which occurs extensively in RA, permitted significant cross-reactivity of RF+ patient sera with fibrinogen in both western blots and ELISAs. Crucially, this reactivity was specific to RF as it was absent in RF- patient and healthy control sera, and could be inhibited by pre-incubation with IgG1 Fc. These studies establish fibrinogen as a common target for both RF and ACPAs, and suggest a new mechanism in RF-mediated autoimmune diseases wherein RF may act as a precursor from which the ACPA response evolves.

The mediating role of cutaneous sensitivity within neonatal psychoneuroimmunology.

Preliminary results of this study have been presented at the ICIS Conferences held in Atlanta, 1998; a Summary of results has been quoted in Adamson-Macedo (1997; 1998). OBJECTIVES: Despite knowledge that preterm infants in intensive care are in distress and need to be provided with appropriate intervention, studies with ventilated babies are still rare particularly during their first weeks of life. This study tested the hypothesis that cutaneous stimulation in the form of TAC-TIC therapy, involving only light stroking and NOT massage or kinesthetic massage, has a mediating role in eliciting beneficial psychoneuroimmunological coactions in the ventilated preterm during the first week of post-natal life. METHODS: A repeated measure, counterbalanced design, was used to collect data twice daily for three consecutive days. This intervention was compared with a control condition consisting of a period of spontaneous activity during which the same infants lay alone with no intervention taking place. For the first time, monitoring facilities were made available for immunological, physiological and behavioral responses to be assessed simultaneously before and after intervention and before and after spontaneous activities. RESULTS. A one tailed t-test indicated that the cutaneous intervention resulted in significantly more episodes of beneficial coactions than matched sessions of spontaneous activity. CONCLUSION: It is suggested that the sensory nerves endings in the skin receive the stimulation from the stroking actions; consequently impulses are being sent via afferent nerve fibers to the limbic system where the sensation is interpreted, by 68% of the neonates, as being comforting or not distressing.

Detection of secretory immunoglobulin A (SIgA) in saliva of ventilated and non-ventilated preterm neonates.

The very young preterm neonate has multiple immune deficiencies which may increase his or her vulnerability to infection. Secretory Immunoglobulin A (SIgA) plays an important role in the protection of epithelial surfaces exposed to the external environment; nevertheless controversy exists with regards to the ontogeny of SIgA in newborns and especially the preterm neonate. The objective was to investigate if SIgA could be detected in the saliva of very/extremely low birthweight neonates (V/ELBW). A total of 707 samples which were collected twice daily (morning and afternoon) for three consecutive days were obtained from sixty-eight preterm neonates (mean gestational age 28 weeks; conceptional age ranged from 25-35 weeks). A repeated measures design was used. Total concentration of SIgA was determined from unstimulated saliva by an Enzyme Linked Immunosorbant Assay technique. Results indicated that SIgA was detectable in the early postnatal period in the saliva of both ventilated preterms who were receiving intravenous total parenteral nutrition (TPN) and non-ventilated preterms. A 3-way repeated measures Analysis of Variance (ANOVA) showed no significant effect from 'before' and 'after' samples during a period of spontaneous activity, time and day of sampling. A significant effect of mode of nutrition was found; neonates who were receiving expressed breast milk had significantly higher concentrations of SIgA than those infants receiving TPN (df=3, F=14.27, p<0.0001). These results have implications for the care of the preterm neonate in intensive care.