Objective: To investigate the relationship between positive anti-Ro/Sjögren syndrome antigen type A (SSA) antibody and anti-La/Sjögren syndrome antigen type B (SSB) antibody in pregnant women and neonatal adverse outcomes. Methods: This study was a retrospective study, and 145 deliveries of 136 anti-Ro/SSA and anti-La/SSB antibody positive pregnant women were selected who had prenatal examination and delivered in Peking University First Hospital from January 2017 to June 2022. According to whether adverse neonatal outcomes occurred, 145 deliveries were divided into adverse outcome group (26 cases) and no adverse outcome group (119 cases). According to the time when anti-Ro/SSA and anti-La/SSB antibodies were found positive, 145 deliveries were divided into the antibody positive during pregnancy group (69 cases) and the pre-pregnancy antibody positive group (76 cases). The pregnancy outcomes, treatment and maternal and infant antibody levels of pregnant women between the adverse outcome group and no adverse outcome group, between antibody positive during pregnancy group and the pre-pregnancy antibody positive group were compared. Results: (1) Most of the pregnant women with positive anti-Ro/SSA and anti-La/SSB antibodies were diagnosed as undifferentiated connective tissue disease, accounting for 40.4% (55/136), followed by Sjogren's syndrome (25.0%, 34/136), systemic lupus erythematosus (23.5%, 32/136), antiphospholipid antibody syndrome (6.6%, 9/136), idiopathic thrombocytopenic purpura (1.5%, 2/136), and 4 cases were not diagnosed. (2) The titers of anti-Ro/SSA and anti-La/SSB antibodies in the first trimester and the second trimester were compared, and there were no statistical significances (all P>0.05). (3) The proportion of high level anti-Ro/SSA antibody (>100 kU/L), positive level of anti-La/SSB antibody and positive rate of anti-La/SSB antibody in the adverse outcome group were higher than those in the no adverse outcome group, and the birth weight of newborns and live birth rate in the adverse outcome group were lower than that in the no adverse outcome group, all with statistical significances (all P<0.05). The anti-Ro/SSA antibody level, the proportion of drug treatment (hydroxychloroquine, glucocorticoid, gamma globulin), the incidence of fetal growth restriction (FGR), the rate of preterm birth, and the positive level of anti-Ro/SSA and anti-La/SSB antibodies in newborns were compared between the two groups, and there were no statistically significant differences (all P>0.05). (4) The anti-Ro/SSA antibody level of pregnant women in the pre-pregnancy antibody positive group, the proportion of hydroxychloroquine and glucocorticoid treatment, and the anti-Ro/SSA antibody positive rate of newborns were higher, while the incidence of FGR and gamma globulin treatment rate of newborns in the antibody positive during pregnancy group were higher, respectively, and the differences were statistically significant (all P<0.05). The levels of anti-La/SSB antibodies in pregnant women, anti-Ro/SSA and anti-La/SSB antibodies in newborns, the positive rate of anti-La/SSB antibodies in newborns and the incidence of adverse outcomes were compared between the antibody positive during pregnancy group and the pre-pregnancy antibody positive group, and there were no statistical significances (all P>0.05). Conclusions: High concentrations of anti-Ro/SSA antibodies and co-positive anti-La/SSB antibodies during pregnancy may increase the incidence of adverse neonatal outcomes. There is no significant difference in the incidence of adverse neonatal outcomes between antibody positive pregnant women and antibody positive pregnant women who were first found during pregnancy after comprehensive treatment in the rheumatology and immunology department.
Infant, Newborn ; Humans ; Female ; Pregnancy ; Sjogren's Syndrome/drug therapy* ; Pregnant Women ; Hydroxychloroquine/therapeutic use* ; Retrospective Studies ; Glucocorticoids ; Premature Birth/epidemiology* ; Lupus Erythematosus, Systemic/drug therapy* ; Pregnancy Outcome ; gamma-Globulins

A fusion protein containing a tetanus toxin peptide, a tuftsin peptide and a SARS-CoV-2S protein receptor-binding domain (RBD) was prepared to investigate the effect of intramolecular adjuvant on humoral and cellular immunity of RBD protein. The tetanus toxin peptide, tuftsin peptide and S protein RBD region were connected by a flexible polypeptide, and a recombinant vector was constructed after codon optimization. The recombinant S-TT-tuftsin protein was prepared by prokaryotic expression and purification. BALB/c mice were immunized after mixed with aluminum adjuvant, and the humoral and cellular immune effects were evaluated. The recombinant S-TT-tuftsin protein was expressed as an inclusion body, and was purified by ion exchange chromatography and renaturated by gradient dialysis. The renaturated protein was identified by Dot blotting and reacted with serum of descendants immunized with SARS-CoV-2 subunit vaccine. The results showed that the antibody level reached a plateau after 35 days of immunization, and the serum antibody ELISA titer of mice immunized with recombinant protein containing intramolecular adjuvant was up to 1:66 240, which was significantly higher than that of mice immunized with S-RBD protein (P < 0.05). At the same time, the recombinant protein containing intramolecular adjuvant stimulated mice to produce a stronger lymphocyte proliferation ability. The stimulation index was 4.71±0.15, which was significantly different from that of the S-RBD protein (1.83±0.09) (P < 0.000 1). Intramolecular adjuvant tetanus toxin peptide and tuftsin peptide significantly enhanced the humoral and cellular immune effect of the SARS-CoV-2 S protein RBD domain, which provideda theoretical basis for the development of subunit vaccines for SARS-CoV-2 and other viruses.
Adjuvants, Immunologic ; Aluminum ; Animals ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19/prevention & control* ; COVID-19 Vaccines/genetics* ; Humans ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins/genetics* ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics* ; Tetanus Toxin ; Tuftsin ; Vaccines, Subunit ; Viral Vaccines

OBJECTIVE: To analyze the clinical characteristics and pregnancy outcomes of pregnant women complicated with coronavirus disease 2019 (COVID-19). METHODS: The clinical data of 3 pregnant women with COVID-19 admitted to the First Affiliated Hospital of Zhejiang University School of Medicine from January 19 to February 10, 2020 were retrospectively analyzed. RESULTS: There was one case in the first-trimester pregnancy (case 1), one in the second-trimester pregnancy (case 2) and one in third-trimester pregnancy (case 3). Cough, fever, fatigue, lung imaging changes were the main manifestations. The white cell count, lymphocyte percentage had no significantly changes in case 1 and case 3, while the levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IL-6 and IL-10 elevated. The lymphocyte count and lymphocyte percentage decreased and the inflammatory indicators significantly increased in case 2. All patients were treated with antiviral, antitussive, oxygen inhalation; case 3 received glucocorticoids, case 2 with severe illness received glucocorticoids and additionally gamma globulin. All three cases were cured and discharged. Case 1 with early pregnancy chose to terminate pregnancy after discharge; case 2 chose to continue pregnancy without obstetric complications; and case 3 had cesarean section delivery due to abnormal fetal heart monitoring. CONCLUSIONS The report shows that COVID-19 in pregnancy women could be cured with active treatment, and the maternal and fetal outcomes can be satisfactory.
Antiviral Agents ; therapeutic use ; Betacoronavirus ; isolation & purification ; Cesarean Section ; Coronavirus Infections ; complications ; drug therapy ; Female ; Glucocorticoids ; therapeutic use ; Humans ; Oxygen ; therapeutic use ; Pandemics ; Pneumonia, Viral ; complications ; drug therapy ; Pregnancy ; Pregnancy Complications, Infectious ; drug therapy ; pathology ; Pregnancy Outcome ; Retrospective Studies ; Treatment Outcome ; gamma-Globulins ; therapeutic use

OBJECTIVE: To investigate the curative effect of simply hormone and combined gamma globulin and thrombopoietin(TPO) on primary immune thrombocytopenia(PITP). METHODS: 100 patients with PITP were divided into simply drug groups, and combined drug group each for 50 cases. The patients in single drug group were given simply hormone therapy, the patients in combined drug group were given gamma globulin and thrombopoietin. The levels of TPO, platelet activating factor (PAF) were detected by DAS-ELISA. The differences of clinical curative effect, clinical indicators, biochemical indexes and adverse reactions between the two groups were compared. RESULTS: The total effective rate of combined drug group (90.00%) was obviously higher than that in single drug group (66.00%)(P<0.05). Amount of platelet infusion in combined drug group was obviously less than that in single drug group, platelet recovery time and effect onset time in combined drug group were significantly shorter than those in single drug group, and the maintaining time in combined drug group was obviously longer than that in single drug group. At the same time, the platelet peak in combined drug group was higher than that in single drug group (P<0.05). The levels of TPO, PAF between the two groups did not show statisticall significant differences before treatment (P>0.05), however, the above-mentioned indexes of two groups after treatment were lower than those before treatment (P<0.05), among them, the indexes in combined drug group were obviously lower ttan those in sigle drug group (P<0.05). The adverse reaction and mortality rate between the two groups did not show statistically significant differences(P>0.05), the recurrence rate in combined drug group(2%) was obviously lower than that in single group(14.00%) (P<0.05). CONCLUSION The curative effect of hormone, as well as gamma globulin combined with TPO to treat PITP are satisfying, can obviously improve the levels of TPO, PAF, and the drug safety is higher. but the efficacy of combined drug is surperior to single drug.
Humans ; Immunoglobulins, Intravenous ; Purpura, Thrombocytopenic, Idiopathic ; Thrombopoietin ; gamma-Globulins

Three dogs were evaluated for severe hyperproteinemia and hyperglobulinemia secondary to Leishmania infantum. Double filtration plasmapheresis (DFPP) was performed in two dogs at days 1, 2, and 6 after presentation. The third dog received DFPP at days 1 and 3 after presentation and eleven hemodialysis treatments. Significant reduction in serum total protein (p < 0.0001), alpha-1 (p = 0.023), alpha-2 (p = 0.018), gamma globulins (p = 0.0105), and a significant increase in albumin/globulin ratio (p = 0.0018) were found. DFPP may be a promising therapeutic technique for rapid resolution of signs of hyperproteinemia in dogs affected by L. infantum.
Animals ; Dogs ; Filtration ; gamma-Globulins ; Leishmania infantum ; Leishmania ; Plasmapheresis ; Renal Dialysis

A 37-year-old female presented to our hospital with a history of bleeding episodes (excessive bleeding after tooth extraction, gum bleeding, easy bruising, and excessive menstruation) and severe thrombocytopenia (2,000/µL). She had no family history of bleeding tendency or thrombocytopenia. No peripheral lymphadenopathy or splenomegaly was noted. The patient's white blood cell count was normal; hemoglobin was 9.7 g/dL. A peripheral blood smear showed markedly decreased platelets, with occasional giant or large platelets. Bone marrow examination found increased megakaryocytes. The patient also complained of hearing difficulty; a hearing test indicated sensory-neural hearing impairment. Her thrombocytopenia was refractory to treatment with glucocorticosteroids, intravenous gamma-globulin, and danazol. In the 13 years following her initial presentation, the patient required anti-hypertensive treatment, a hearing-aid for progressive hearing loss, and started maintenance kidney dialysis. Her clinical history of refractory thrombocytopenia, progressive hearing impairment, and renal failure suggested myosin heavy chain 9 gene-related congenital syndrome (Epstein syndrome), which was confirmed by the presence of a heterozygous deletion mutation, c.221_223del, (p.Lys74del) in peripheral leukocyte deoxyribonucleic acid.
Adult ; Bone Marrow Examination ; Danazol ; Dialysis ; DNA ; Female ; gamma-Globulins ; Gingiva ; Hearing ; Hearing Loss ; Hearing Loss, Sensorineural ; Hearing Tests ; Hemorrhage ; Humans ; Kidney ; Leukocyte Count ; Leukocytes ; Lymphatic Diseases ; Megakaryocytes ; Myosin Heavy Chains ; Renal Insufficiency ; Renal Insufficiency, Chronic ; Sequence Deletion ; Splenomegaly ; Thrombocytopenia* ; Tooth Extraction

PURPOSE: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by mutations in the Bruton's tyrosine kinase (Btk) gene. The aim of this study was to investigate the clinical manifestations, molecular features, and treatment status of XLA in Korean patients at Seoul National University Children's Hospital. METHODS: Fourteen Korean boys with XLA showing serum agammaglobulinemia, non-detectable to less than 2% of peripheral B-cells, and mutation of the Btk gene were enrolled. We observed the clinical features, laboratory findings, status of treatment, and complications in these XLA patients. RESULTS: All XLA patients had a history of recurrent bacterial infections before diagnosis, and 20% of them had a neutropenia. Of the XLA patients 35.7% had a family history of XLA and 75% of their mothers were carriers. Btk gene analysis showed variable gene mutations in Xq22 including 9 amino acid substitutions, 3 frameshifts, 1 premature stop codon, and 1 splice defect. After intravenous immunoglobulin replacement therapy, infection episodes decreased, but complications such as bronchiectasis and chronic sinusitis remained. CONCLUSIONS: In patients less than 4 years of age with recurrent infection, analysis of serum gamma globulin levels and the Btk gene are recommended for the early diagnosis of XLA and for the appropriate prevention of recurrent infection.
Agammaglobulinemia* ; Amino Acid Substitution ; B-Lymphocytes ; Bacterial Infections ; Bronchiectasis ; Codon, Nonsense ; Diagnosis ; Early Diagnosis ; gamma-Globulins ; Humans ; Immunoglobulins ; Immunoglobulins, Intravenous ; Mothers ; Neutropenia ; Protein-Tyrosine Kinases ; Seoul ; Sinusitis

PURPOSE: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by mutations in the Bruton's tyrosine kinase (Btk) gene. The aim of this study was to investigate the clinical manifestations, molecular features, and treatment status of XLA in Korean patients at Seoul National University Children's Hospital. METHODS: Fourteen Korean boys with XLA showing serum agammaglobulinemia, non-detectable to less than 2% of peripheral B-cells, and mutation of the Btk gene were enrolled. We observed the clinical features, laboratory findings, status of treatment, and complications in these XLA patients. RESULTS: All XLA patients had a history of recurrent bacterial infections before diagnosis, and 20% of them had a neutropenia. Of the XLA patients 35.7% had a family history of XLA and 75% of their mothers were carriers. Btk gene analysis showed variable gene mutations in Xq22 including 9 amino acid substitutions, 3 frameshifts, 1 premature stop codon, and 1 splice defect. After intravenous immunoglobulin replacement therapy, infection episodes decreased, but complications such as bronchiectasis and chronic sinusitis remained. CONCLUSIONS: In patients less than 4 years of age with recurrent infection, analysis of serum gamma globulin levels and the Btk gene are recommended for the early diagnosis of XLA and for the appropriate prevention of recurrent infection.
Agammaglobulinemia* ; Amino Acid Substitution ; B-Lymphocytes ; Bacterial Infections ; Bronchiectasis ; Codon, Nonsense ; Diagnosis ; Early Diagnosis ; gamma-Globulins ; Humans ; Immunoglobulins ; Immunoglobulins, Intravenous ; Mothers ; Neutropenia ; Protein-Tyrosine Kinases ; Seoul ; Sinusitis

OBJECTIVETo investigate the clinical efficacy and safety of intravenous injection of low-dose versus high-dose gamma globulin combined with glucocorticoid pulse therapy in the treatment of children with moderate/severe acute Guillain-Barré syndrome (GBS).

METHODSA total of 100 children with moderate/severe acute GBS were randomly assigned to low-dose group (n=48) and high-dose group (n=52). The children in the low-dose and high-dose groups were treated with 0.2 g/(kg · d) and 0.4 g/(kg · d) gamma globulin respectively combined with methylprednisolone. The two groups were compared in terms of the time to improvements of symptoms after treatment, serum levels of inflammatory factors, proportion of children undergoing invasive ventilation, treatment response rate, and adverse events.

RESULTSAfter 5 days of treatment, the low- and high-dose groups had significant reductions in serum levels of tumor necrosis factor-α, interleukin-6, and C-reactive protein, and there were no significant differences in the reductions of these markers between the two groups. There were no significant differences between the two groups in the time to recovery of respiratory muscle paralysis, time to an improvement in muscle strength of one grade, time to recovery of sensory disturbance, and length of hospital stay. There was no significant difference in the treatment response rate between the low- and high-dose groups (90% vs 92%). There were also no significant differences in the incidence rates of pyrexia, headache, nausea, and palpitation between the two groups.

CONCLUSIONSLow-dose versus high-dose gamma globulin combined with methylprednisolone pulse therapy have comparable clinical efficacy and safety in the treatment of children with moderate/severe acute GBS.

Adolescent ; C-Reactive Protein ; analysis ; Child ; Child, Preschool ; Female ; Guillain-Barre Syndrome ; drug therapy ; Humans ; Length of Stay ; Male ; Methylprednisolone ; administration & dosage ; Tumor Necrosis Factor-alpha ; blood ; gamma-Globulins ; administration & dosage

OBJECTIVETo study the clinical effect of high-dose gamma globulin pulse therapy for abdominal Henoch-Schönlein purpura (HSP).

METHODSThirty-three children with abdominal HSP were randomly assigned to dexamethasone group (15 children) and gamma globulin group (18 children). The children in the dexamethasone group were treated with dexamethasone and conventional treatment, and those in the gamma globulin group were treated with high-dose gamma globulin pulse therapy in addition to the conventional treatment. Clinical outcome and recurrence rate were observed in both groups.

RESULTSCompared with the dexamethasone group, the gamma globulin group had a significantly shorter onset time of rash, a significantly shorter time to complete regression of rash, a significantly shorter time to abdominal pain remission, and a significantly shorter time to disappearance of bloody stool, as well as comparable time to vomiting remission and length of hospital stay. The gamma globulin group had a significantly higher response rate than the dexamethasone group (95% vs 65%; P<0.05) and a significantly lower recurrence rate within 6 months than the dexamethasone group (5.6% vs 33.3%; P<0.05).

CONCLUSIONSHigh-dose gamma globulin pulse therapy has a marked clinical effect in the treatment of abdominal HSP. It is safe and reliable and has a low recurrence rate, and therefore, it holds promise for clinical application.

Child ; Child, Preschool ; Dexamethasone ; adverse effects ; therapeutic use ; Female ; Humans ; Male ; Purpura, Schoenlein-Henoch ; drug therapy ; Recurrence ; gamma-Globulins ; administration & dosage ; adverse effects