Gastrointestinal dysfunction associated with autoimmune glial fibrillary acidic protein astrocytopathy.

BACKGROUND AND

OBJECTIVES

Gastrointestinal (GI) dysfunction has been reported in autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). However, GI dysfunction in GFAP-A has not been sufficiently investigated. This study aimed to analyze the clinical features of GFAP-A patients with GI dysfunction and explore potential pathogenic mechanisms.

METHODS

From January 1, 2016, to April 30, 2024, patients diagnosed with GFAP-A based on CSF GFAP-IgG positivity at the Third Affiliated Hospital of Sun Yat-sen University were enrolled. Clinical parameters and GI dysfunction assessed by the I-FEED scoring system were collected. Pathological examination was performed in a subset of patients. And the preliminary role of GFAP-IgG in the enteric plexus was investigated.

RESULTS

Among 92 enrolled individuals (male:female = 68:24; median age 39.5 years), gastrointestinal dysfunction occurred in 72 cases (78.3%). Manifestations included constipation in 38 cases (41.3%), paralytic ileus in 30 cases (32.6%), fecal incontinence in 3 cases (3.26%), and diarrhea in 1 case (1.09%). Severe GI dysfunction (I-FEED score ≥ 6) was associated with higher disease severity (admission mRS 5.0 vs. 3.0, p < 0.001), longer hospitalization (21.5 vs. 15.5 days, p = 0.029), increased ICU admission (50.0% vs. 10.5%, p < 0.001), higher rates of respiratory failure, autonomic dysfunction, and infections, worse CSF profiles (elevated protein, leukocytosis, hypoglycorrhachia). Pathological analysis revealed prominent CD8⁺ and CD4⁺ T-cell infiltration in the colonic wall and a specific loss of GFAP⁺ enteric glia. Furthermore, we demonstrated that anti-GFAP-IgG derived from the cerebrospinal fluid (CSF) of GFAP-A patients binds specifically to the enteric plexus within mouse colonic tissues.

CONCLUSIONS

Our findings collectively suggest that severe GI dysfunction could be a marker of disease severity and poor prognosis in GFAP-A, and indicate that its potential mechanism may involve the specific binding of anti-GFAP-IgG to the enteric plexus and subsequent enteric glia loss.