Chronic histiocytic intervillositis: manifestation of placental alloantibody-mediated rejection

Benachi, Alexandra; Rabant, Marion; Martinovic, Jéléna; Bouchghoul, Hanane; Vivanti, Alexandre J.; Léon, Juliette; Grünenwald, Anne; Roumenina, Lubka; Celton, J.L.; Bessières, Bettina; Taupin, Jean‐Luc

doi:10.1016/j.ajog.2021.06.051

Cited by 19 publications

(34 citation statements)

References 37 publications

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“…While the presence of C4d reinforces the theory that CHI results from humoral immune rejection, it does not of course identify the causative placental antigen. Benachi et al confirmed diffuse villous staining for C4d in recurrent CHI and also noted focal deposition of the C5b-9 membrane attack complex, suggesting localised complement activation (83). Figure 4 shows C4d deposition in CHI.…”

Section: Chi: Evidence For An Immune Aetiologymentioning

confidence: 84%

“…However, other evidence implies that the primary problem is maternal, particularly in the case of CHI. Firstly, CHI carries a recurrence rate of up to 100% and worsens in successive pregnancies (36,(81)(82)(83). Secondly, when women with recurrent pregnancy loss due to CHI undergo IVF with their own oocyte and their partner's sperm, followed by implantation into a surrogate, CHI does not recur (84).…”

Section: Chronic Placental Inflammation and Autoimmune Diseasementioning

confidence: 99%

“…In the absence of an infectious cause, attention should focus on an immune-mediated pathophysiology. Parallels with transplant immunology have led some groups to describe VUE, CHI and MPFD as analogous to maternal "rejection" of the fetal semi-allograft (13,72,83,108,109). However, unlike solid organ allografts, serial sampling of the placenta during pregnancy is impossible given the associated risks to both mother and fetus.…”

Section: Chronic Placental Inflammation and Infectionmentioning

confidence: 99%

“…However, this response is transient: if the mouse subsequently becomes pregnant with an embryo that expresses the same antigen, these specific T-cell populations undergo clonal deletion to maintain tolerance to the developing fetus (123). By contrast, in humans, fetal-specific T cells are detectable several years after delivery (83,124,125). This persistence of anti-fetal T cells could account for the recurrence and worsening clinical severity observed in CHI and VUE, but murine models could not support investigation of this hypothesis.…”

Section: Insights From Animal Studiesmentioning

confidence: 99%

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Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome

2022

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Chronic inflammatory placental disorders are a group of rare but devastating gestational syndromes associated with adverse pregnancy outcome. This review focuses on three related conditions: villitis of unknown etiology (VUE), chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition (MPFD). The hallmark of these disorders is infiltration of the placental architecture by maternal immune cells and disruption of the intervillous space, where gas exchange between the mother and fetus occurs. Currently, they can only be detected through histopathological examination of the placenta after a pregnancy has ended. All three are associated with a significant risk of recurrence in subsequent pregnancies. Villitis of unknown etiology is characterised by a destructive infiltrate of maternal CD8+ T lymphocytes invading into the chorionic villi, combined with activation of fetal villous macrophages. The diagnosis can only be made when an infectious aetiology has been excluded. VUE becomes more common as pregnancy progresses and is frequently seen with normal pregnancy outcome. However, severe early-onset villitis is usually associated with fetal growth restriction and recurrent pregnancy loss. Chronic histiocytic intervillositis is characterised by excessive accumulation of maternal CD68+ histiocytes in the intervillous space. It is associated with a wide spectrum of adverse pregnancy outcomes including high rates of first-trimester miscarriage, severe fetal growth restriction and late intrauterine fetal death. Intervillous histiocytes can also accumulate due to infection, including SARS-CoV-2, although this infection-induced intervillositis does not appear to recur. As with VUE, the diagnosis of CHI requires exclusion of an infectious cause. Women with recurrent CHI and their families are predisposed to autoimmune diseases, suggesting CHI may have an alloimmune pathology. This observation has driven attempts to prevent CHI with a wide range of maternal immunosuppression. Massive perivillous fibrin deposition is diagnosed when >25% of the intervillous space is occupied by fibrin, and is associated with fetal growth restriction and late intrauterine fetal death. Although not an inflammatory disorder per se, MPFD is frequently seen in association with both VUE and CHI. This review summarises current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology and potential prophylaxis against recurrence in these three chronic inflammatory placental syndromes.

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Section: Chi: Evidence For An Immune Aetiologymentioning

confidence: 84%

Section: Chronic Placental Inflammation and Autoimmune Diseasementioning

confidence: 99%

Section: Chronic Placental Inflammation and Infectionmentioning

confidence: 99%

Section: Insights From Animal Studiesmentioning

confidence: 99%

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Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome

2022

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“…Of note, recent studies suggest that MPVF and CHI are phenotypes showing some overlap and that distinct clinical subsets may exist with different IHC profiles. 46 , 47 …”

Section: Discussionmentioning

confidence: 99%

Diffuse and Localized SARS-CoV-2 Placentitis

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Ravishankar

Bagby

et al. 2022

American Journal of Surgical Pathology

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Coronavirus disease 2019 (COVID-19) infection in pregnancy has been associated with preterm delivery and preeclampsia. A less frequent and underrecognized complication is extensive placental infection which is associated with high rates of perinatal morbidity and mortality. The frequency, early pathogenesis, and range of lesions associated with this infection are poorly understood. We conducted a population-based study of placental pathology from all mothers with COVID-19 (n=271) over an 18-month period delivering within our health system. The overall prevalence of diffuse severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) placentitis, as defined by typical histology and immunohistochemical (IHC) staining for SARS-CoV-2 spike protein, was 14.8/1000, but increased to 59/1000 in preterm births. We also identified 3 cases with isolated small foci of localized SARS-CoV-2 placentitis, characterized by focal perivillous fibrin and intervillositis, which illustrate the early pathogenesis and suggest that infection may be contained in some cases. Two other placental lesions were more common in mothers with COVID-19, high-grade maternal vascular malperfusion in preterm deliveries and high-grade chronic villitis at term (5/5 cases tested of the latter were negative by IHC for SARS-CoV-2). Additional investigation of diffuse and localized SARS-CoV-2 placentitis by IHC showed loss of BCL-2, C4d staining in surrounding villi, and an early neutrophil-predominant intervillous infiltrate that later became dominated by monocyte-macrophages. We propose a model of focal infection of syncytiotrophoblast by virally infected maternal leukocytes leading to loss of BCL-2 and apoptosis. Infection is then either contained by surrounding fibrinoid (localized) or initiates waves of aponecrosis and immune activation that spread throughout the villous parenchyma (diffuse).

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A comprehensive analysis of the association between placental pathology and recurrent preterm birth

Suresh

Freedman

Hirsch

et al. 2022

American Journal of Obstetrics and Gynecology

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Chronic histiocytic intervillositis: manifestation of placental alloantibody-mediated rejection

Cited by 19 publications

References 37 publications

Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome

Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome

Diffuse and Localized SARS-CoV-2 Placentitis

A comprehensive analysis of the association between placental pathology and recurrent preterm birth

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