Anti-phospholipid antibodies (APA) like anti-cardiolipin antibodies (ACA) and anti-β2glycoprotien (anti-β2GP) are important cause of venous and arterial thrombosis and other occlusive vascular diseases. The prevalen...Anti-phospholipid antibodies (APA) like anti-cardiolipin antibodies (ACA) and anti-β2glycoprotien (anti-β2GP) are important cause of venous and arterial thrombosis and other occlusive vascular diseases. The prevalence of these antibodies in SLE patients at the time of diagnosis is not known in Indian SLE patients. This study was conducted to evaluate the prevalence of ACA and anti-β2GP autoantibodies in SLE patients and to correlate them with disease activity and immune parameters such as C3, C4 and CRP levels. where 85 SLE patients referred from Rheumatology Department, KEM hospital, Mumbai were studied. SLE disease activity was evaluated by SLE Disease Activity Index (SLEDAI) score at the time of evaluation. All patients studied were in an active stage of disease of which 37.6% patients had renal disorders, which were categorized as Lupus Nephritis (LN) and 62.3% patients did not show any renal manifestations (non-LN). ACA and anti-β2GP autoantibodies, to IgG and IgM subclasses were tested by ELISA. C3, C4 and CRP levels were detected by nephelometer. It was observed that 12.9% patients were IgG-ACA and IgM-ACA positive and ACA positivity was noted more among LN group Anti-β2GP autoantibody positivity was 27.1% for IgG and 31.8% for IgM., IgG-anti-β2GP antibodies were slightly higher in non-LN patients, whereas a higher incidence of IgM-anti-β2GP antibodies were detected in LN patients. Hence detection both ACA and anti-β2GP antibodies along with associated immune parameters were helpful to evaluate their possible association with disease severity in SLE patients. A long term follow up of patients having ACA and anti-β2GP antibodies without thrombotic event is also needed to detect their possible thrombotic event in future along with their clinical presentation.展开更多
Antibody blocking enzyme linked immunosorbent assays, respectively detecting antibodies to Hantaan virus nucleoprotein (NPAb) and glycoprotein GZ (G,Ab), were developed using monoclonal antibody L133, L13r3, LV48A and...Antibody blocking enzyme linked immunosorbent assays, respectively detecting antibodies to Hantaan virus nucleoprotein (NPAb) and glycoprotein GZ (G,Ab), were developed using monoclonal antibody L133, L13r3, LV48A and LVZB28B NPAb and GZAb in 291 serum samples from 65 patientswith kemorrkagic fever with renal syudrome (HFRS) were detfrmlned by these methods. The positive rates or NPAb were 90N on day 2-3 and 100 % on day 8-9 arter onset of disease, respectively.NPAb titers Increased during fever period and reached Peak levels during kypotensive and oliguric periods of HFRS. It was suggested that NPAb might be an important component Involved in the immunopathogenlc lin'alrmeut of HFRS and the detection of NPAb might be useful for the early diagnosis or HFRS. The I,osltlve rates and titers of GZAh were very low during the rirst three periods,namely rever, hypoteuslve and ollgurlc periods, and reached high levels during the convalescent period. GRAb titers were negatively related to the I,rotelnurla levels during the course of HFRS. It wasIndicated that GZAb might be the main component or neutralizing autlhodles to Hantaan virus Infection and the efrlclent production or GZAb was a good marker ror predicting the recovery and betterprognosis of HFRS.展开更多
BACKGROUND Atypical optic neuritis,consisting of neuromyelitis optica spectrum disorders(NMOSD)or myelin oligodendrocyte glycoprotein antibody disease(MOGAD),has a very similar presentation but different prognostic im...BACKGROUND Atypical optic neuritis,consisting of neuromyelitis optica spectrum disorders(NMOSD)or myelin oligodendrocyte glycoprotein antibody disease(MOGAD),has a very similar presentation but different prognostic implications and longterm management strategies.Vascular and metabolic factors are being thought to play a role in such autoimmune neuro-inflammatory disorders,apart from the obvious immune mediated damage.With the advent of optical coherence tomography angiography(OCTA),it is easy to pick up on these subclinical macular microvascular and structural changes.AIM To study the macular microvascular and structural changes on OCTA in atypical optic neuritis.METHODS This observational cross-sectional study involved 8 NMOSD and 17 MOGAD patients,diagnosed serologically,as well as 10 healthy controls.Macular vascular density(MVD)and ganglion cell+inner plexiform layer thickness(GCIPL)were studied using OCTA.RESULTS There was a significant reduction in MVD in NMOSD and MOGAD affected as well as unaffected eyes when compared with healthy controls.NMOSD and MOGAD affected eyes had significant GCIPL thinning compared with healthy controls.NMOSD unaffected eyes did not show significant GCIPL thinning compared to healthy controls in contrast to MOGAD unaffected eyes.On comparing NMOSD with MOGAD,there was no significant difference in terms of MVD or GCIPL in the affected or unaffected eyes.CONCLUSION Although significant microvascular and structural changes are present on OCTA between atypical optic neuritis and normal patients,they could not help in differentiating between NMOSD and MOGAD cases.展开更多
The CD4 binding site(CD4bs) of envelope glycoprotein(Env) is an important conserved target for anti-human immunodeficiency virus type 1(HIV-1) neutralizing antibodies. Neutralizing monoclonal antibodies IgG1 b12(b12) ...The CD4 binding site(CD4bs) of envelope glycoprotein(Env) is an important conserved target for anti-human immunodeficiency virus type 1(HIV-1) neutralizing antibodies. Neutralizing monoclonal antibodies IgG1 b12(b12) could recognize conformational epitopes that overlap the CD4 bs of Env. Different virus strains, even derived from the same individual, showed distinct neutralization susceptibility to b12. We examined the key amino acid residues affecting b12 neutralization susceptibility using single genome amplification and pseudovirus neutralization assay. Eleven amino acid residues were identified that affect the sensitivity of Env to b12. Through site-directed mutagenesis, an amino acid substitution at position 182 in the V2 region of Env was confirmed to play a key role in regulating the b12 neutralization susceptibility. The introduction of V182 L to a resistant strain enhanced its sensitivity to b12 more than twofold. Correspondingly, the introduction of L182 V to a sensitive strain reduced its sensitivity to b12 more than tenfold. Amino acid substitution at positions 267 and 346 could both enhance the sensitivity to b12 more than twofold. However, no additive effect was observed when the three site mutageneses were introduced into the same strain, and the sensitivity was equivalent to the single V182 L mutation. CRF07_BC is a major circulating recombinant form of HIV-1 prevalent in China. Our data may provide important information for understanding the molecular mechanism regulating the neutralization susceptibility of CRF07_BC viruses to b12 and may be helpful for a vaccine design targeting the CD4 bs epitopes.展开更多
AIM: To describe the clinical characteristics and treatments associated with antibody positive optic neuropathies including anti-myelin oligodendrocyte glycoprotein(MOG) and anti-aquaporin 4(AQP4), alongside diagnosti...AIM: To describe the clinical characteristics and treatments associated with antibody positive optic neuropathies including anti-myelin oligodendrocyte glycoprotein(MOG) and anti-aquaporin 4(AQP4), alongside diagnostic modalities, investigations, and outcomes. METHODS: A cross-sectional single-centre retrospective case series consisting of 16 patients including 12 antiMOG positive patients and 4 anti-AQP4 positive patients. Each of these patients had clinical signs and symptoms of optic neuritis and consisted of all patients who had a positive blood antibody result in our centre. Clinical findings including presence of a relative afferent pupillary defect, colour vision and disc assessment were recorded. Structured clinical exam and multimodal imaging was undertaken sequentially on each. Optical coherence tomography(OCT) scanning was preformed to examine the correlation between ganglion cell layer(GCL) thickness and visual acuity(VA) at presentation and as a determinant of final visual outcome in both groups. Initial and long-term treatment is also summarised. RESULTS: A total of 16 patients were included in the study consisting of 12 anti-MOG and 4 anti-AQP4 positive patients. Nine of the 16 patients were female and the average age of onset was 29.2 y in the MOG group and 42 y in the AQP4 group. There was no statistically significant correlation(Pearson correlation) between GCL thickness and presenting and final VA [r(10)=0.081, P=0.08 and r(10)=0.089, P=0.34 respectively]. The same statistical analysis was performed for the correlation between retinal nerve fibre layer(RNFL) and VA and similar outcomes wereobserved [r(10)=0.04, P=0.22 and r(10)=0.09, P=0.04]. No correlation was seen for initial RNFL thickness and final visual outcome in this group either [r(2)=0.19, P=0.38]. Visual field testing and radiological findings for each group are described. CONCLUSION: No correlation between initial VA or RNFL and final visual outcome is identified. A broad range of visual field and radiographic findings are identified, a consensus on treatment of neuromyelitis optica spectrum disorders and anti-MOG positive optic neuropathies has yet to be accepted but initial high dose immunosuppression followed by low dose maintenance therapy is favoured.展开更多
Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a newly identified member of the coronavirus family that has caused the coronavirus disease 2019 (COVID-19) pandemic. This rapidly evolving and unrelenting...Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a newly identified member of the coronavirus family that has caused the coronavirus disease 2019 (COVID-19) pandemic. This rapidly evolving and unrelenting SARS-CoV-2has disrupted the lives and livelihoods of millions worldwide. As of 23 August 2021, a total of 211,373,303 COVID-19cases have been confirmed globally with a death toll of 4,424,341. A strong understanding of the infection pathway of SARS-CoV-2, and how our immune system responds to the virus is highly pertinent for guiding the development and improvement of effective treatments. In this review, we discuss the current understanding of neutralising antibodies(NAbs) and their implications in clinical practice. The aspects include the pathophysiology of the immune response,particularly humoral adaptive immunity and the roles of NAbs from B cells in infection clearance. We summarise the onset and persistence of IgA, IgM and IgG antibodies, and we explore their roles in neutralising SARS-CoV-2, their persistence in convalescent individuals, and in reinfection. Furthermore, we also review the applications of neutralising antibodies in the clinical setting—from predictors of disease severity to serological testing to vaccinations, and finally in therapeutics such as convalescent plasma infusion.展开更多
The results of research work completed in recent years in the authors’ laboratory withmonoclonal antibodies (McAbs) against herpes simplex virus (HSV) are reported in this paper as fol-lows.(1) Eighteen hybridoma cel...The results of research work completed in recent years in the authors’ laboratory withmonoclonal antibodies (McAbs) against herpes simplex virus (HSV) are reported in this paper as fol-lows.(1) Eighteen hybridoma cell lines steadily producing McAbs against HSV were established byhybridoma technic.(2) The mechanisms of neutralization in vitro and animal protection in vivo medi-ated by different McAbs were investigated.(3) A method of detecting virus antigua was developedwith the McAbs.(4) Tne isolates of virus were typed and antigenically analysed by type-specificand type-common McAbs.(5) HSV antigen in clinical spectimens was detected and directly typed byan ELISA method coating with type-specific and type-common McAb.(6) The target antigens ofMcAbs were identified,purified,and their genes were localized.(7) Experimental rabbitHSV keratitis was treated with McAbs.展开更多
In this study, we investigated the clinical relevance of anti-myelin antibodies in patients with neuromyelitis optica (NMO);titers of antibodies against myelin oligodendrocyte glycoproteins, proteolipid proteins and m...In this study, we investigated the clinical relevance of anti-myelin antibodies in patients with neuromyelitis optica (NMO);titers of antibodies against myelin oligodendrocyte glycoproteins, proteolipid proteins and myelin basic proteins were measured in the sera of patients with NMO and compared to healthy controls, as well as to patients with other diseases. The frequency of presence of anti-myelin antibodies in patients with NMO was significantly higher than that in healthy and diseased controls. The expanded disability status scale scores correlated with the titers of the anti-myelin antibodies. Patients with anti-myelin antibody exhibited other autoantibodies significantly more frequently than patients without the antibody. Anti-myelin antibodies may be useful markers for predicting severe clinical courses in patients with NMO.展开更多
文摘Anti-phospholipid antibodies (APA) like anti-cardiolipin antibodies (ACA) and anti-β2glycoprotien (anti-β2GP) are important cause of venous and arterial thrombosis and other occlusive vascular diseases. The prevalence of these antibodies in SLE patients at the time of diagnosis is not known in Indian SLE patients. This study was conducted to evaluate the prevalence of ACA and anti-β2GP autoantibodies in SLE patients and to correlate them with disease activity and immune parameters such as C3, C4 and CRP levels. where 85 SLE patients referred from Rheumatology Department, KEM hospital, Mumbai were studied. SLE disease activity was evaluated by SLE Disease Activity Index (SLEDAI) score at the time of evaluation. All patients studied were in an active stage of disease of which 37.6% patients had renal disorders, which were categorized as Lupus Nephritis (LN) and 62.3% patients did not show any renal manifestations (non-LN). ACA and anti-β2GP autoantibodies, to IgG and IgM subclasses were tested by ELISA. C3, C4 and CRP levels were detected by nephelometer. It was observed that 12.9% patients were IgG-ACA and IgM-ACA positive and ACA positivity was noted more among LN group Anti-β2GP autoantibody positivity was 27.1% for IgG and 31.8% for IgM., IgG-anti-β2GP antibodies were slightly higher in non-LN patients, whereas a higher incidence of IgM-anti-β2GP antibodies were detected in LN patients. Hence detection both ACA and anti-β2GP antibodies along with associated immune parameters were helpful to evaluate their possible association with disease severity in SLE patients. A long term follow up of patients having ACA and anti-β2GP antibodies without thrombotic event is also needed to detect their possible thrombotic event in future along with their clinical presentation.
文摘Antibody blocking enzyme linked immunosorbent assays, respectively detecting antibodies to Hantaan virus nucleoprotein (NPAb) and glycoprotein GZ (G,Ab), were developed using monoclonal antibody L133, L13r3, LV48A and LVZB28B NPAb and GZAb in 291 serum samples from 65 patientswith kemorrkagic fever with renal syudrome (HFRS) were detfrmlned by these methods. The positive rates or NPAb were 90N on day 2-3 and 100 % on day 8-9 arter onset of disease, respectively.NPAb titers Increased during fever period and reached Peak levels during kypotensive and oliguric periods of HFRS. It was suggested that NPAb might be an important component Involved in the immunopathogenlc lin'alrmeut of HFRS and the detection of NPAb might be useful for the early diagnosis or HFRS. The I,osltlve rates and titers of GZAh were very low during the rirst three periods,namely rever, hypoteuslve and ollgurlc periods, and reached high levels during the convalescent period. GRAb titers were negatively related to the I,rotelnurla levels during the course of HFRS. It wasIndicated that GZAb might be the main component or neutralizing autlhodles to Hantaan virus Infection and the efrlclent production or GZAb was a good marker ror predicting the recovery and betterprognosis of HFRS.
文摘BACKGROUND Atypical optic neuritis,consisting of neuromyelitis optica spectrum disorders(NMOSD)or myelin oligodendrocyte glycoprotein antibody disease(MOGAD),has a very similar presentation but different prognostic implications and longterm management strategies.Vascular and metabolic factors are being thought to play a role in such autoimmune neuro-inflammatory disorders,apart from the obvious immune mediated damage.With the advent of optical coherence tomography angiography(OCTA),it is easy to pick up on these subclinical macular microvascular and structural changes.AIM To study the macular microvascular and structural changes on OCTA in atypical optic neuritis.METHODS This observational cross-sectional study involved 8 NMOSD and 17 MOGAD patients,diagnosed serologically,as well as 10 healthy controls.Macular vascular density(MVD)and ganglion cell+inner plexiform layer thickness(GCIPL)were studied using OCTA.RESULTS There was a significant reduction in MVD in NMOSD and MOGAD affected as well as unaffected eyes when compared with healthy controls.NMOSD and MOGAD affected eyes had significant GCIPL thinning compared with healthy controls.NMOSD unaffected eyes did not show significant GCIPL thinning compared to healthy controls in contrast to MOGAD unaffected eyes.On comparing NMOSD with MOGAD,there was no significant difference in terms of MVD or GCIPL in the affected or unaffected eyes.CONCLUSION Although significant microvascular and structural changes are present on OCTA between atypical optic neuritis and normal patients,they could not help in differentiating between NMOSD and MOGAD cases.
基金supported by grants from National Science and Technology Major Project(2012ZX10004701)
文摘The CD4 binding site(CD4bs) of envelope glycoprotein(Env) is an important conserved target for anti-human immunodeficiency virus type 1(HIV-1) neutralizing antibodies. Neutralizing monoclonal antibodies IgG1 b12(b12) could recognize conformational epitopes that overlap the CD4 bs of Env. Different virus strains, even derived from the same individual, showed distinct neutralization susceptibility to b12. We examined the key amino acid residues affecting b12 neutralization susceptibility using single genome amplification and pseudovirus neutralization assay. Eleven amino acid residues were identified that affect the sensitivity of Env to b12. Through site-directed mutagenesis, an amino acid substitution at position 182 in the V2 region of Env was confirmed to play a key role in regulating the b12 neutralization susceptibility. The introduction of V182 L to a resistant strain enhanced its sensitivity to b12 more than twofold. Correspondingly, the introduction of L182 V to a sensitive strain reduced its sensitivity to b12 more than tenfold. Amino acid substitution at positions 267 and 346 could both enhance the sensitivity to b12 more than twofold. However, no additive effect was observed when the three site mutageneses were introduced into the same strain, and the sensitivity was equivalent to the single V182 L mutation. CRF07_BC is a major circulating recombinant form of HIV-1 prevalent in China. Our data may provide important information for understanding the molecular mechanism regulating the neutralization susceptibility of CRF07_BC viruses to b12 and may be helpful for a vaccine design targeting the CD4 bs epitopes.
文摘AIM: To describe the clinical characteristics and treatments associated with antibody positive optic neuropathies including anti-myelin oligodendrocyte glycoprotein(MOG) and anti-aquaporin 4(AQP4), alongside diagnostic modalities, investigations, and outcomes. METHODS: A cross-sectional single-centre retrospective case series consisting of 16 patients including 12 antiMOG positive patients and 4 anti-AQP4 positive patients. Each of these patients had clinical signs and symptoms of optic neuritis and consisted of all patients who had a positive blood antibody result in our centre. Clinical findings including presence of a relative afferent pupillary defect, colour vision and disc assessment were recorded. Structured clinical exam and multimodal imaging was undertaken sequentially on each. Optical coherence tomography(OCT) scanning was preformed to examine the correlation between ganglion cell layer(GCL) thickness and visual acuity(VA) at presentation and as a determinant of final visual outcome in both groups. Initial and long-term treatment is also summarised. RESULTS: A total of 16 patients were included in the study consisting of 12 anti-MOG and 4 anti-AQP4 positive patients. Nine of the 16 patients were female and the average age of onset was 29.2 y in the MOG group and 42 y in the AQP4 group. There was no statistically significant correlation(Pearson correlation) between GCL thickness and presenting and final VA [r(10)=0.081, P=0.08 and r(10)=0.089, P=0.34 respectively]. The same statistical analysis was performed for the correlation between retinal nerve fibre layer(RNFL) and VA and similar outcomes wereobserved [r(10)=0.04, P=0.22 and r(10)=0.09, P=0.04]. No correlation was seen for initial RNFL thickness and final visual outcome in this group either [r(2)=0.19, P=0.38]. Visual field testing and radiological findings for each group are described. CONCLUSION: No correlation between initial VA or RNFL and final visual outcome is identified. A broad range of visual field and radiographic findings are identified, a consensus on treatment of neuromyelitis optica spectrum disorders and anti-MOG positive optic neuropathies has yet to be accepted but initial high dose immunosuppression followed by low dose maintenance therapy is favoured.
基金supported by the National Medical Research Council,Singapore (NMRC COVID19RF2-0002)。
文摘Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a newly identified member of the coronavirus family that has caused the coronavirus disease 2019 (COVID-19) pandemic. This rapidly evolving and unrelenting SARS-CoV-2has disrupted the lives and livelihoods of millions worldwide. As of 23 August 2021, a total of 211,373,303 COVID-19cases have been confirmed globally with a death toll of 4,424,341. A strong understanding of the infection pathway of SARS-CoV-2, and how our immune system responds to the virus is highly pertinent for guiding the development and improvement of effective treatments. In this review, we discuss the current understanding of neutralising antibodies(NAbs) and their implications in clinical practice. The aspects include the pathophysiology of the immune response,particularly humoral adaptive immunity and the roles of NAbs from B cells in infection clearance. We summarise the onset and persistence of IgA, IgM and IgG antibodies, and we explore their roles in neutralising SARS-CoV-2, their persistence in convalescent individuals, and in reinfection. Furthermore, we also review the applications of neutralising antibodies in the clinical setting—from predictors of disease severity to serological testing to vaccinations, and finally in therapeutics such as convalescent plasma infusion.
文摘The results of research work completed in recent years in the authors’ laboratory withmonoclonal antibodies (McAbs) against herpes simplex virus (HSV) are reported in this paper as fol-lows.(1) Eighteen hybridoma cell lines steadily producing McAbs against HSV were established byhybridoma technic.(2) The mechanisms of neutralization in vitro and animal protection in vivo medi-ated by different McAbs were investigated.(3) A method of detecting virus antigua was developedwith the McAbs.(4) Tne isolates of virus were typed and antigenically analysed by type-specificand type-common McAbs.(5) HSV antigen in clinical spectimens was detected and directly typed byan ELISA method coating with type-specific and type-common McAb.(6) The target antigens ofMcAbs were identified,purified,and their genes were localized.(7) Experimental rabbitHSV keratitis was treated with McAbs.
文摘In this study, we investigated the clinical relevance of anti-myelin antibodies in patients with neuromyelitis optica (NMO);titers of antibodies against myelin oligodendrocyte glycoproteins, proteolipid proteins and myelin basic proteins were measured in the sera of patients with NMO and compared to healthy controls, as well as to patients with other diseases. The frequency of presence of anti-myelin antibodies in patients with NMO was significantly higher than that in healthy and diseased controls. The expanded disability status scale scores correlated with the titers of the anti-myelin antibodies. Patients with anti-myelin antibody exhibited other autoantibodies significantly more frequently than patients without the antibody. Anti-myelin antibodies may be useful markers for predicting severe clinical courses in patients with NMO.
