Neutrophil function in pregnancy and rheumatoid arthritis

Abstract

Background-Pregnancy exerts suppressive eVects on rheumatoid arthritis (RA). An attenuation in neutrophil function in late pregnancy which may explain this amelioration has previously been reported. Objective-A longitudinal investigation of neutrophil activity in healthy pregnant women (n=9) and pregnant patients with RA (n=9), compared with age matched non-pregnant patients with RA (n=12) and healthy controls (n=22). Methods-Neutrophil activation was measured in response to the physiological receptor agonists, n-formyl-methionylleucyl-phenylalanine (fMLP) and zymosan activated serum (ZAS). Superoxide anion production (respiratory burst) was determined by lucigenin enhanced chemiluminescence (LUCL); secondary granule lactoferrin release by enzyme linked immunosorbent assay (ELISA); and CD11b, CD18, and CD62L expression by flow cytometric analysis. Results-Stimulated neutrophil LUCL was significantly reduced in both pregnant women with RA and healthy pregnant women in the second (fMLP 43% and 69%, ZAS 43% and 59%, respectively) and third trimesters (fMLP 24% and 44%, ZAS 32% and 38%, respectively). Responses returned to normal within eight weeks of delivery and unstimulated levels remained unchanged throughout pregnancy. Basal and stimulated CD11b, CD18, and CD62L expression showed no variations throughout gestation for both pregnancy groups. Likewise, stimulated lactoferrin release and plasma lactoferrin remained unchanged. Certain morphological diVerences in RA neutrophils were highlighted by the flow cytometric analysis. Moreover, resting neutrophils and stimulated cells from patients with RA, including pregnant subjects, showed a marked increase in LUCL, but a reduction in CD11b, CD18, and CD62L. Low dose prednisolone and methylprednisolone had no eVect on neutrophil parameters over the period of treatment with non-steroidal anti-inflammatory drugs. Conclusion-The attenuation to neutrophil respiratory burst in both healthy and RA pregnancies may oVer an explanation for the pregnancy induced remission of this inflammatory disorder.

Neutrophils induce proangiogenic T cells with a regulatory phenotype in pregnancy

“…Although activated neutrophils have been implicated in the pathophysiology of preeclampsia (22), very little is known about the physiological role of quiescent neutrophils in pregnancy, despite their increased circulating numbers during gestation (23). Our observations in the human system in vitro indicate a potential protective role for quiescent neutrophils in pregnancy.…”

Physiological Changes in Hematological Parameters During Pregnancy

“…Increased production of RBCs to meet the demands of pregnancy, reasonably explains why there is an increased MCV (due to a higher proportion of young RBCs which are larger in size). However, MCV does not change significantly during pregnancy and a hemoglobin concentration \9.5 g/dL in association with a mean corpuscular volume \84 fl probably indicates co-existent iron deficiency or some other pathology [6].…”

Variation in erythrocyte and leukocyte counts before and after normal vaginal delivery

“…The RBC indices change little in pregnancy. [19] The initial fall in RBC count during puerperium may account for compensatory hemodilution which occurs following delivery. In the present study, predelivery RBC count was 4.4 ± 0.5 millions/cumm of blood which goes in line with the studies by Gebreweld on "Hematological profile of pregnant women at St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia" showing predelivery RBC count of 4.46 ± 0.47.…”

“…[24,25] In the first trimester of pregnancy, there is an absolute monocytosis but decreases as gestation advances. Monocytes by infiltrating the decidual tissue (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) th week of gestation) possibly, through PGE 2 -mediated immunosuppression help in preventing fetal allograft rejection. [26] In pregnancy, monocyte to lymphocyte ratio is markedly increased.…”