Prevalence of antibodies to ganglioside and Hep 2 in Gaucher, Niemann – Pick type C and Sanfilippo diseases

Abstract

Lysosomal Storage Diseases (LSDs) are rare genetic diseases, the majority of which are caused by specific lysosomal enzyme deficiencies and all are characterized by malfunctioning lysosomes. Lysosomes are key regulators of many different cellular processes and are vital for the function of the immune system. Several studies have shown the coexistence of LSDs and immune abnormalities. In this study, we investigated the presence of autoantibodies in the plasma of patients with Gaucher disease (GD; n = 6), Sanfilippo Syndrome B (SFB; n = 8) and Niemann – Pick type C disease (NPC; n = 5) before and following Miglustat treatment ( n = 3). All were examined for antibodies to antigens of Hep-2 cells and antiganglioside antibodies (AGSA). No autoantibodies were detected in GD patients. 3/8 SFB patients showed only AGSA (2/3 IgM / IgG; 1/3 IgG), 3/8 only anti-Sm E/F and 2/8 showed both IgM / IgG or IgG AGSA and anti-Sm E/F. 3/5 NPC patients showed AGSA (2/3 IgM and IgG, 1/3 IgM) and one anti-Sm E/F and IgM AGSA. Following treatment one patient with no AGSA developed IgM AGSA and two with both IgG and IgM showed only IgG AGSA. In our study, investigating similar numbers of patients, autoantibodies were observed in NPC and SFB patients but not in GD patients. Our findings suggest that, independently of the development of an autoimmune disease in patients with LSDs, there seems to be an autoimmune activation that differs in different disorders. Further studies including more patients, also at different stages of disease and treatment, are needed in order to get further insight into the immune irregularities associated with different LSDs and their significance.

The role of brain innate immune response in lysosomal storage disorders: fundamental process or evolutionary side effect?

“…2). The production of autoantibodies against the progressively accumulated gangliosides has been shown in the genetic disorders GM2 gangliosidoses [90], NPC, and Sanfilippo syndrome B [91], supporting the premise that elevation in host ganglioside levels can lead to antiganglioside antibody generation (Fig. 2).…”

Exploring Pro-Inflammatory Immunological Mediators: Unraveling the Mechanisms of Neuroinflammation in Lysosomal Storage Diseases

“…A similar condition is thought to occur in lysosomal storage disease due to the genetic defects and the resultant excess peripheral organs (e.g., liver, spleen, lung, heart, kidneys, and lymph nodes) accumulation of distinct substrates (e.g., GC in Gaucher, Gb3 and Lyso Gb3 in Fabry, GM1 in GM1gangliosidosis, GM2 in Tay–Sachs and Sandhoff, Sph, GlycSph, Sm, and Ch in Niemann–Pick type C, Cer in Farber, GalSph in Krabbe, and CEs and TGs in Wolman diseases), which lead to the cellular activation and increased production of the growth factors, such as MCSF, GCSF, and GMCSF, which mobilize hematopoietic progenitors into the peripheral circulation [ 229 , 230 , 231 , 232 ]. This is supported here by the elevated level of growth factors (e.g., MCSF, GCSF, and GMCSF), chemoattractants (C3a, C5a, CCL2, CCL3, CCL4, CCL5, CCL10, CCL11, CCL12, CXCL1, CXCL9, CXCL10, CXCL11, and CXCL13), and the increased presence of MOs, granulocytes, MOs-differentiated Mϕs and DCs, T cells, NK cells, NKT cells, antibodies producing plasma B cells in circulation and the peripheral organs of the different lysosomal storage diseases [ 6 , 7 , 11 , 36 , 76 , 112 , 113 , 157 , 158 , 165 , 176 , 186 , 194 , 203 , 204 , 222 , 233 , 234 , 235 , 236 , 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 ]. The increased migration of several of such pro-inflammatory mediators into circulation may serve as a new set of biomarkers for diagnosing lysosomal storage diseases and evaluating the effectiveness of novel medications in clinical trials.…”

“…The cerebella and cerebral cortex of Npc1 −/− mice have shown elevated levels of IFNα, IFNβ, TNFα, IL1α, IL1β, and the loss of Purkinje cells [ 157 , 161 , 162 , 163 , 164 ]. The plasma of patients with Niemann–Pick type C disease showed the presence of IgG and IgM antibodies to GM1, GM2, and GM3 [ 165 ]. The postmortem brain tissue (e.g., frontal cortex and cerebellum) from patients with NPC1 disease showed elevated levels of C3 and C4 [ 163 ].…”

Case Report: Be Aware of “New” Features of Niemann–Pick Disease: Insights From Two Pediatric Cases

“…Many studies have reported an association between autoimmune phenomena and LSDs ( Rigante et al, 2017 ). Recently, autoantibodies in NPC have been reported in several studies ( Dimitriou et al, 2019 ; Chu et al, 2021 ). Herein, we reported two clinical cases of NPC in the form of cholestatic jaundice combined with immune activation in early infancy diagnosed by genetic analysis.…”