Background/Purpose: In 2013 we have described the first patients with a novel autoinflammatory disease manifested in 4 children with recurrent Guillain-Barre syndrome and hemolytic anemia in infancy due to loss of function of CD59 (Nevo et al., Blood). Since then, additional 3 mutations were recognized and clinical course of 14 patients was documented. Eculizumab was started in all patients and polezimab in one patient and clinical course was evaluated using clinical scores questionnaires and follow-up and laboratory evaluation.

Methods: The 4 mutations, p.Cys64Tyr, p.Asp24Val, p.Asp24Valfs*, and p.Ala16Alafs*, were identified in 14 individuals with CD59 malfunction. All 14 presented with recurrent Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy, recurrent strokes, and chronic hemolysis. The molecular consequences of the 4 mutations and their effects on CD59 expression, localization, glycosylation, degradation, secretion, and function was evaluated and treatment with eculizumab or pozelimab was established with a follow-up up to 7 years. All patients responded well to eculizumab. One patient developed hypersensitivity to eculizumab that was successfully switched to pozelimab with similar clinical and in vitro complement inhibition effect.

In this study we aimed to determine whether  chronic hemolysis and cumulative doses of steroid and IV IgG were reduced, and neurological deficits compared to those observed before treatment, were ameliorated. Treatment response was evaluated every 4 weeks over 6-8 years and included examination with gross motor scoring ASIA and INCAT, laboratory examination, and SF-12 fulfillment. Neurological relapses and the cumulative dose of IVIG and/or corticosteroids before and after initiation of treatment were documented. RBCs and neutrophils were stained to evaluate C5b-9 deposition. ClinicalTrials.gov, NCT01579838.

Results: All patients responded well to eculizumab. One patient developed hypersensitivity to eculizumab that was successfully switched to pozelimab with similar clinical and in vitro complement inhibition effect.

A 7-8 years follow-up in 4 patients showed a dramatic and significant neurological amelioration in the upper limbs and trunk with a more modest amelioration in the lower limbs was observed and maintained in all patients. Corticosteroids and immunoglobulin treatment, which had been used extensively prior to eculizumab initiation, was completely stopped. No patient suffered a relapse during the treatment period despite infections, and there were no hospital admissions apart fro 2 admissions due to reduced drug administration and allergic reaction. Decreased deposition of C3bi and C5b-9 on RBCs and neutrophils was documented (p< 0.0001). The SF-12 health questionnaires indicated significant improvement (p< 0.003).

Conclusion: The autoinflammatory disease seen with CD59 congenital malfunction was well controlled by eculizumab and pozelimab

« Back to ACR Convergence 2020

ACR Meeting Abstracts - https://acrabstracts.org/abstract/8-years-follow-up-of-a-novel-autoinflammatory-disease-cd59-malfunction-causes-hemolytic-anemia-recurrent-guillain-barre-syndrome-and-strokes-in-pediatric-populations-and-respond-well-to-eculizumab/