Clinical features, genetic variations and enzyme replacement therapy in five Chinese patients with Fabry disease / 中华肾脏病杂志

Objective:To analyze the efficacy and safety of enzyme replacement therapy (ERT) in Chinese patients with Fabry disease.Methods:A retrospective analysis of the clinical manifestations, genetic variations, family screening, treatments and adverse reactions was conducted in five patients with Fabry disease admitted to the First Affiliated Hospital of Zhejiang University College of Medicine from July 2020 to May 2021. The dosage of agalsidase β was 1 mg/kg by intravenous pump once every 2 weeks.Results:Five male patients with median age of 37 years old (29-51 years old) were diagnosed based on clinical features, family history, α-galactosidase A (α-Gal A) activity, genetic analysis results and kidney biopsy. The clinical manifestations varied in these five patients. All patients had abnormal electrocardiogram, abnormal cardiac ultrasonography and abnormal urinalysis results, three experienced acroparaesthesia during childhood (one patient had persistent pain until adulthood), three had cutaneous angiokeratoma, four had renal insufficiency, four had hypohidrosis, four had diarrheas, four had cornea verticillata and two had high-frequency hearing loss. Two missense mutations of the GLA gene were identified: c.272T>C(p.I91T) and c.868A>G(p.Met290Val). Two nonsense mutations were c.1024C>T(p.Arg342*) and c.838C>T(p.Gln280*). Furthermore, the frameshift mutation c.348del p.(Ile117Phefs*4) was detected, which was not included in the known database, presented with classical Fabry disease. There was no serious adverse reaction during agalsidase β infusion in 5 patients. ERT reduced the plasma globotriaosylsphingosine (lyso-GL-3) levels after treatment of 2-10 months ( P<0.05), and the long-term diarrhea symptom were significantly improved. Conclusions:The clinical manifestations of Fabry disease are varied. Severe adverse events rarely occur in patients treated with short-term ERT. Plasma lyso-GL-3 levels decrease significantly after treatment.

Chemokine receptor CXCR5 supports solitary intestinal lymphoid tissue formation, B cell homing, and induction of intestinal IgA responses.

Solitary intestinal lymphoid tissue (SILT) comprises a spectrum of phenotypically diverse lymphoid aggregates interspersed throughout the small intestinal mucosa. Manifestations of SILT range from tiny lymphoid aggregates almost void of mature lymphocytes to large structures dominated by B cells. Large SILT phenotypically resemble a single Peyer's patch follicle, suggesting that SILT might contribute to intestinal humoral immune responses. In this study, we track the fate of individual SILT in vivo over time and analyze SILT formation and function in chemokine receptor CXCR5-deficient mice. We show that, in analogy to Peyer's patches, formation of SILT is invariantly determined during ontogeny and depends on CXCR5. Young CXCR5-deficient mice completely lack SILT, suggesting that CXCR5 is essential for SILT formation during regular postnatal development. However, microbiota and other external stimuli can induce the formation of aberrant SILT distinguished by impaired development of B cell follicles in CXCR5-deficient mice. Small intestinal transplantation and bone marrow transplantation reveal that defect follicle formation is due to impaired B cell homing. Moreover, oral immunization with cholera toxin or infection with noninvasive Salmonella fail to induce efficient humoral immune responses in CXCR5-deficient mice. Bone marrow transplantation of CXCR5-deficient recipients with wild-type bone marrow rescued B cell follicle formation in SILT but failed to restore full humoral immune responses. These results reveal an essential role of CXCR5 in Peyer's patch and SILT development and function and indicate that SILT do not fully compensate for the lack of Peyer's patches in T cell-dependent humoral immune responses.

Mycophenolate mofetil combined with low dose prednisone in the treatment for adults with minimal change nephrotic syndrome and concomitant HBsAg positive / 中华肾脏病杂志

Objective To assess the safety and efficacy of mycophenolate mofetil (MMF) combined with low dose corticosteroid in the treatment of adults with minimal change nephrotic syndrome and concomitant HBsAg positive (MCNS-HBsAg). Methods Thirty adults with MCNS-HBsAg were enrolled in this prospective study and were assigned to two groups. The MMF group (n=14) received low dose of prednisone combined with MMF (MMF 1.0 to 2.0 g/d patients of Pred group versus 35.7% patients of MMF group. 43.8% patients of Pred group versus 21.4% patients of MMF group received lamivudine therapy. Elevation of alanine aminotransferase(ALT) ocurred in 50% patients of Pred group and 28.6% patients of MMF group. The complete remission (CR) rate after 24 weeks treatment was 11/14 in Pred group versus 10/12 in MMF group. 6/11 patients of the Pred group and 4/10 patients of the MMF group who achieved CR experienced relapses during follow-up. Conclusions Use of MMF combined with low dose prednisone is as effective as conventional prednisone regimen in treating adults with MCNS-HBsAg. The MMF protocol seems to be superior in HBV reactivation to conventional prednisone protocol.

THE EFFECT OF IRON SUPPLEMENTATION ON PREGNANT WOMEN AND NEWBORNS WITH IRON DEFICIENCY / 营养学报

Objective: To study iron deficiency (ID) of newborns caused by ID in pregnant women and the effect of iron supplementation. [WT5FZ]Methods: [WT5BZ]Forty four pregnant women were divided into control and iron groups randomly and began to take placebo or iron during median phase of pregnancy. Several indices including serum iron (SI), total iron binding capacity (TIBC), transferrin saturation (TS) and serum ferritin (SF) were measured. Hemoglobin concentrations were obtained from clinical records. [WT5FZ]Results: [WT5BZ]The Hb,SI,TS and SF of newborns in control group were lower than those of newborns in iron group. The incidence of anemia and insufficiency of iron store of newborns in control group were 80% and 54.5% respectively, which were higher than those of newborns in iron group. Except SI of newborns and SF of pregnant women, the SI, TS and SF of newborns were positively related to those of pregnant mothers. Fewer women in iron group suffering from iron deficiency anemia by the end of pregnancy compared to the control were noted. From median phase to the end of pregnancy the Hb, SI, TS and SF of pregnant women in control group remained constant or lower, while the Hb, SI and TS of the pregnant women in iron group got higher and their SF didnt decrease progressively. [WT5FZ]Conclusion: [WT5BZ]The relationship between the nutritional status of iron of pregnant women and newborns is closely related. ID of pregnant woman can lead to the ID of her newborn. Iron supplementation can reduce ID of pregnant women and newborns.