BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

OBJECTIVE: To investigate the effectiveness of tibial transverse transport (TTT) in treating Wagner grade 3-4 type 2 diabetic foot ulcers and analyze dynamic changes in immunoglobulin levels. METHODS: The clinical data of 68 patients with Wagner grade 3-4 type 2 diabetic foot ulcers treated with TTT between May 2022 and September 2023 was retrospectively analyzed. The cohort included 49 males and 19 females, aged 44-91 years (mean, 67.3 years), with 40 Wagner grade 3 and 28 grade 4 ulcers. The duration of type 2 diabetes ranged from 5 to 23 years, with an average of 10 years. The number of wound healing cases, healing time, amputation cases, death cases, and complications were observed and recorded. Serum samples were collected at 6 key time points [1 day before TTT and 3 days, 7 days (the first day of upward transverse transfer), 14 days (the first day of downward transverse transfer), 21 days (the first day after the end of transfer), 36 days (the first day after the removal of the transfer device)], and the serum immunoglobulin levels were detected by flow cytometry including immunoglobulin G (IgG), IgA, IgM, IgE, complement C3 (C3), C4, immunoglobulin light chain κ (KAP), immunoglobulin light chain λ (LAM). RESULTS: All the 68 patients were followed up 6 months. Postoperative pin tract infection occurred in 3 cases and incision infection in 2 cases. Amputation occurred in 5 patients (7.4%) at 59-103 days after operation, and 8 patients (11.8%) died at 49-77 days after operation; the wounds of the remaining 55 patients (80.9%) healed in 48-135 days, with an average of 80 days. There was no recurrence of ulcer, peri-osteotomy fracture, or local skin necrosis during follow-up. The serum immunoglobulin levels of 55 patients with wound healing showed that the levels of IgG and IgM decreased significantly on the 3rd and 7th day after operation compared with those before operation ( P<0.05), and gradually returned to the levels before operation after 14 days, and reached the peak on the 36th day. IgA levels continued to decrease with time, and there were significant differences at all time points when compared with those before operation ( P<0.05). The level of IgE significantly decreased at 21 days after operation compared with that before operation ( P<0.05), while it was higher at other time points than that before operation, but the difference was not significant ( P>0.05). The level of C3 showed a clear treatment-related increase, which was significantly higher on the 7th, 14th, and 21st days after operation than that before operation ( P<0.05), and the peak appeared on the 14th day. The change trend of C4 level was basically synchronous with that of C3, but the amplitude was smaller, and the difference was significant at 7 and 14 days after operation compared with that before operation ( P<0.05). There was no significant difference in KAP/LAM between different time points before and after operation ( P>0.05). CONCLUSION TTT can accelerate wound healing, effectively treat diabetic foot ulcer, and reduce amputation rate, and has definite effectiveness. The potential mechanisms of TTT in the treatment of diabetic foot ulcers include the dynamic regulation of IgG, IgA, IgM, and IgE levels to balance the process of inflammation and repair, and the periodic increase of C3 and C4 levels may promote tissue cleaning, angiogenesis, and anti-infection defense.
Humans ; Male ; Female ; Middle Aged ; Aged ; Diabetic Foot/immunology* ; Wound Healing ; Adult ; Retrospective Studies ; Aged, 80 and over ; Treatment Outcome ; Tibia/transplantation* ; Diabetes Mellitus, Type 2/complications* ; Amputation, Surgical ; Immunoglobulins/blood* ; Immunoglobulin G/blood*

BACKGROUND: Recent studies have reported that glucosamine (GlcN) showed therapeutic effects in allergic diseases such as asthma and rhinitis, and its mechanisms include the suppression of T helper type 2 immune responses and the nuclear factor-κB pathway. OBJECTIVE: We aimed to investigate the effect of GlcN on atopic dermatitis (AD) in an animal model. METHODS: Twenty-five BALB/c mice were divided into five groups (groups A~E). Group A was the phosphate-buffered saline (PBS)-treated group without AD induction. Group B was the PBS control group with AD induction. Groups C to E were the AD induction groups, which were treated with three different doses of GlcN (10 mg, 20 mg, and 40 mg, respectively). Histopathological examination was performed after GlcN administration. Interleukin (IL)-4, IL-13, and IL-17 cytokine levels were measured by enzyme-linked immunosorbent assay using skin biopsy specimens. Serum total immunoglobulin E (IgE) concentrations were measured before and after administration with GlcN or PBS. RESULTS: Clinical dermatitis scores decreased with increasing GlcN dose (p<0.001). Concentrations of tissue IL-13 and IL-17 decreased after GlcN administration (each group: p=0.002 and p<0.001, respectively), but the concentrations of tissue IL-4 did not show differences across groups. Serum IgE levels tended to be lower after GlcN administration (p=0.004). Histopathological scores were not significantly different among groups B~E (p=0.394). CONCLUSION: GlcN improved AD symptoms and decreased tissue IL-13, IL-17, and serum total IgE levels in an animal model.
Allergy and Immunology ; Animals ; Anti-Allergic Agents ; Asthma ; Biopsy ; Dermatitis ; Dermatitis, Atopic ; Enzyme-Linked Immunosorbent Assay ; Glucosamine ; Immunoglobulin E ; Immunoglobulins ; Interleukin-13 ; Interleukin-17 ; Interleukin-4 ; Interleukins ; Mice ; Models, Animal ; Rhinitis ; Skin ; Therapeutic Uses

BACKGROUND: We developed skin prick test (SPT) reagents for common inhalant allergens that reflected the real exposure in Korea. The study aim was to evaluate diagnostic usefulness and allergen potency of our inhalant SPT reagents in comparison with commercial products. METHODS: We produced eight common inhalant allergen SPT reagents using total extract (Prolagen): Dermatophagoides farinae, Dermatophagoides pteronyssinus, oak, ragweed, mugwort, Humulus japonicus pollens, as well as cat and dog allergens. We compared the newly developed reagents with three commercially available SPT reagents (Allergopharma, Hollister-Stier, Lofarma). We measured total protein concentrations, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), major allergen concentration, and biological allergen potencies measured by immunoglobulin E (IgE) immunoblotting and ImmunoCAP inhibition test. RESULTS: Diagnostic values of these SPT reagents were expressed as positivity rate and concordance rate of the results from ImmunoCAP allergen-specific IgE test in 94 allergic patients. In vitro analysis showed marked differences in protein concentrations, SDS-PAGE features, major allergen concentrations, and biological allergen potencies of four different SPT reagents. In vivo analysis showed that positive rates and concordance rates of Prolagen® SPT reagents were similar compared to the three commercial SPT reagents. CONCLUSION: The newly developed Prolagen® inhalant SPT reagents are not inferior to the commercially available SPT reagents in allergy diagnosis.
Allergens ; Allergy and Immunology ; Ambrosia ; Animals ; Artemisia ; Cats ; Dermatophagoides farinae ; Dermatophagoides pteronyssinus ; Diagnosis ; Dogs ; Electrophoresis ; Electrophoresis, Polyacrylamide Gel ; Humans ; Humulus ; Hypersensitivity ; Immunoblotting ; Immunoglobulin E ; Immunoglobulins ; In Vitro Techniques* ; Indicators and Reagents* ; Korea ; Methods* ; Pollen ; Skin* ; Sodium

OBJECTIVETo observe the effects of Huaiqihuang granules on the immune function in children with severe Mycoplasma pneumoniae pneumonia.

METHODSPediatric inpatients with severe Mycoplasma pneumoniae pneumonia were randomly divided into Huaiqihuang granule treatment group (n=51) and conventional treatment group (n=47). The Huaiqihuang granule treatment group was orally administered Huaiqihuang granules in addition to the conventional treatment, while the conventional treatment group received conventional treatment only. Levels of serum IgA, IgG, and IgM, percentages of CD4and CD8 T lymphocyte subsets, and CD4/CD8ratio were examined in the two groups. The incidence rate of respiratory tract re-infection within three months following treatment was compared between the two groups.

RESULTSThe levels of serum IgA, IgG, and IgM, the percentage of CD4 T lymphocytes, and the CD4/CD8ratio were significantly higher in the Huaiqihuang granule treatment group than in the conventional treatment group three months after treatment (P<0.05). In contrast, the percentage of CD8T lymphocytes was significantly lower in the Huaiqihuang granule treatment group than in the conventional treatment group (P<0.05). In addition, the incidence rate of respiratory tract re-infection within three months following treatment was significantly lower in the Huaiqihuang granule treatment group than in the conventional treatment group (P<0.05).

CONCLUSIONSHuaiqihuang granules can regulate immune functions and reduce the incidence of short-term respiratory tract re-infection in children with severe Mycoplasma pneumoniae pneumonia.

Adolescent ; CD4-CD8 Ratio ; Child ; Child, Preschool ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Immunoglobulins ; analysis ; Male ; Pneumonia, Mycoplasma ; drug therapy ; immunology ; T-Lymphocyte Subsets ; drug effects ; immunology

The task force of the Korean Society for Reproductive Immunology recommends intravenous immunoglobulin G treatment in women with reproductive failure, including recurrent pregnancy loss and/or repeated implantation failure, who show cellular immune factors such as abnormal natural killer cell levels, natural killer cell cytotoxicity, and/or type 1 T helper immunity.
Abortion, Habitual ; Advisory Committees ; Allergy and Immunology* ; Female ; Humans ; Immunoglobulin G* ; Immunoglobulins* ; Immunologic Factors ; Infertility ; Killer Cells, Natural ; Pregnancy

Recently, the rhinitis work group of the Korean Academy of Asthma, Allergy and Clinical Immunology developed a practice guideline on allergic rhinitis. The group consisted of physicians, pediatricians, and otolaryngologists. Here, the guideline is adapted for clarity and for ease of use by physicians. To manage allergic rhinitis well, accurate diagnosis is most important. In patients with rhinitis symptoms, the first step is to perform a skin prick test to inhalant allergens, and/or to measure allergen-specific immunoglobulin E in serum. Next, allergic rhinitis should be diagnosed upon documenting the association between positive allergens and rhinitis symptoms, via patient history or allergen nasal provocation test. Allergic rhinitis should be differentiated from non-allergic rhinitis, because treatment modalities differ between the two. Allergic rhinitis should be effectively managed with allergen avoidance, pharmacotherapy, allergen immunotherapy, surgical treatment, and/or saline irrigation. Second-generation antihistamines or leukotriene modifiers may be used for mild-to-moderate forms, and intranasal steroids may be effective for moderate-to-severe forms. Allergic rhinitis is closely associated with asthma. Spirometry should be performed initially for asthma diagnosis, if asthma-like symptoms are present.
Allergens ; Allergy and Immunology ; Asthma ; Desensitization, Immunologic ; Diagnosis ; Drug Therapy ; Histamine Antagonists ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulins ; Nasal Provocation Tests ; Rhinitis ; Rhinitis, Allergic* ; Skin ; Spirometry ; Steroids

OBJECTIVETo investigate the risk factors for mother-to-child transmission of hepatitis B virus (HBV) and the efficacy of hepatitis B immunoprophylaxis in children at high risk of hepatitis B.

METHODSA questionnaire survey was performed on 539 HBsAg-positive mothers and their 551 children (aged from 6 months to 5 years) at high risk of hepatitis B. Serum markers of hepatitis B in the children at high risk of hepatitis B were measured. Univariate logistic regression analysis was used to investigate the risk factors for mother-to-child transmission of HBV.

RESULTSThe rate of hepatitis B vaccination in the children at high risk of hepatitis B was 100%, and 96.6% received injections of hepatitis B vaccine and hepatitis B immunoglobulin (HBIG). The HBsAg positive rate showed no significant differences between different age groups. The HBsAb positive rate gradually decreased with the increasing age (P<0.01). The children born to HBsAg- and HBeAg-positive mothers had a significantly higher hepatitis B infection rate than those born to HBsAg-positive mothers (15.1% vs 0.2%; P<0.01). The high-risk children who received hepatitis B vaccination alone had a significantly higher hepatitis B infection rate than those who received both hepatitis B vaccine and HBIG injections (28.6% vs 2.8%; P<0.01).

CONCLUSIONSThe HBsAb positive rate gradually decreases with the increasing age in children at high risk of hepatitis B. Maternal HBsAg and HBeAg positivity and the absence of HBIG combined with hepatitis B vaccine injections for children at high risk of hepatitis B are the risk factors for mother-to-child transmission of HBV.

Child, Preschool ; Female ; Hepatitis B ; etiology ; prevention & control ; Hepatitis B Surface Antigens ; analysis ; Hepatitis B Vaccines ; immunology ; Hepatitis B e Antigens ; analysis ; Humans ; Immunoglobulins ; immunology ; Infant ; Infectious Disease Transmission, Vertical ; prevention & control ; Male ; Risk Factors

OBJECTIVETo investigate the effect of laparoscopic Roux-en-Y gastric bypass on the short-term immune function of type 2 diabetic patients and to explore the correlation between the immune regulatory effect and blood glucose control.

METHODSClinical data of 28 patients with type 2 diabetes mellitus who underwent laparoscopic Roux-en-Y gastric bypass surgery in our hospital during January 2014 to January 2015 were retrospectively collected. Fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), immunoglobulin (IgG, IgA, IgM), T lymphocytes CD3(+), killer T cells CD3(+)CD8(+), helper T cells CD3(+)CD4(+), natural killer(NK) cell subsets CD16(+),CD56(+) and B cell subsets CD19(+),CD45(+) levels were detected and compared between before and after surgery. Correlation of immunoglobulin and immune cell subsets with the level of FBG and HbA1c were examined.

RESULTSAfter operation, FBG and HbA1c decreased significantly from (5.78±1.15) mmol/L to (14.21±1.89) mmol/L, and (9.96±0.97)% to (6.87±0.69)%, respectively (all P<0.05), and immunoglobulin (IgG, IgA, IgM) increased significantly [IgG: from(9.41±1.23) g/L to (12.74±1.61) g/L, IgM: from (1.71±0.22) g/L to (2.43±0.39) g/L, IgA: from (1.25±0.26) g/L to (1.97±0.23) g/L, all P<0.05]. Besides, T lymphocytes CD3(+), killer T cells CD3(+)CD8(+) and B cell subsets CD19(+)CD45(+) elevated significantly as well [T lymphocytes CD3(+): from (55.3±3.8)% to (67.6±4.6)%, killer T cells CD3(+)CD8(+): from (15.6±5.3)% to (28.7±4.2)%, B cell subsets CD19(+)CD45(+): from (8.4±3.7)% to (18.1±4.1)%, respectively, all P <0.05]. There was no significant difference in the expression of helper T cells CD3(+)CD4(+) and natural killer cell subsets CD16(+)CD56(+) between pre-operation and post-operation(all P>0.05). Levels of immunoglobulin (IgG, IgA, IgM), CD4(+)/CD8(+) ratio and B cell subsets were negatively correlated with HbA1c and FBG levels (IgG with FBG: r=-0.865, IgA with FBG: r=-0.887, IgM with FBG: r=-0.902, CD4(+)/CD8(+) with FBG: r=-0.956, CD19(+)CD45(+) with FBG: r=-0.834; IgG with HbA1C: r=-0.859, IgA with HbA1C: r=-0.957, IgM with HbA1C: r=-0.843, CD4(+)/CD8(+) with HbA1C: r=-0.912, CD19(+)CD45(+) and HbA1C: r=-0.885, all P<0.05), but the proportion of NK cells was not significantly correlated with HbA1c and FBG (P>0.05).

CONCLUSIONSLaparoscopic Roux-en-Y gastric bypass has good effect on the immune function of patients with type 2 diabetes mellitus. Improvement of immune function is correlated with the control of FBG and HbA1c.

Blood Glucose ; analysis ; Diabetes Mellitus, Type 2 ; immunology ; surgery ; Gastric Bypass ; Glycated Hemoglobin A ; analysis ; Humans ; Immunoglobulins ; blood ; Laparoscopy ; Lymphocyte Subsets ; immunology ; Postoperative Period ; Retrospective Studies

OBJECTIVEThis study aimed to conduct a preliminary study on the possible role and significance of interleukin (IL)-12 and IL-27 in the pathogeneses of oral lichen planus (OLP).

METHODSThirty cases of patients with OLP (fifteen cases of reticular OLP and fifteen cases of erosive OLP) were enrolled in this study, and twenty cases of healthy people served as controls. Lymphocyte subsets CD3+, CD4+, CD8+, CD19+, and CD16+56 [natural killer cell (NK)] were tested using flow cytometry, and humoral immunity [immunoglobulin (Ig)G, IgA, IgM, C3, C4] were examined using nephelometry assays. IL-12 and IL-27 contents in serum of patients with OLP and normal controls were detected through enzyme linked immunosorbent assay. The correlations between the levels of IL-12, IL-27, immune status, and clinical characteristics of patients with OLP were analyzed, respectively.

RESULTSCD3+, CD4+, and CD8+in patients with OLP were markedly lower than the normal value, whereas CD 19+ of OLP in patients was significantly higher than the normal value (P<0.05). IgM inpatients with OLP was increased, whereas C4 was declined (P<0.05). IL-12 and IL-27 levels showed significant upregulation or ULF patients compared with control groups (P<0.05). Meanwhile, positive correlations existed between IL-12 andIL-27 levels in the serum of patients with OLP (r=0.912, P<0.01). No significant correlations of IL-12 and IL-27 epressions with clinical characteristics of OLP were found (P>0.05). Negative correlations of IL-12 and IL-27 levels with CD16+56(NK) cells were observed (r1 = -0.416, P1 = 0.022; r2 = -0.392, P2=0.032, respectively), whereas a positive correlation existed for IgG (r1=0.445, P1=0.014; n=0.549, P2=0.002, respectively).

CONCLUSIONA cellular immune dysfunction mainly dominate in patients with OLP, accompanied by some degree of humoral-immunity-function disorder. The abnormally high expressions of IL-12 and IL-27 are possibly synergized and promoted inflammation development in OLP. Its promotion takes place through the negatie feedback regulation of humoral immune responses, which are involved in the regulation of immune mechanisms of OLP.

Flow Cytometry ; Humans ; Immunoglobulins ; blood ; Interleukin-12 ; blood ; Interleukin-12 Subunit p35 ; metabolism ; Interleukin-27 ; blood ; Interleukins ; metabolism ; Killer Cells, Natural ; Lichen Planus, Oral ; blood ; immunology