panorama0000ProteomicsLin LiHomo Sapienshttps://panoramaweb.org/g9ah75.urllli26@tulane.eduSchool of Medicine, Tulane UniversityPanoramaPublic<h4>Background</h4>Novel approaches that allow early diagnosis and treatment monitoring of both human immunodeficiency virus-1 (HIV-1) and tuberculosis disease (TB) are essential to improve patient outcomes.<h4>Methods</h4>We developed and validated an immuno-affinity liquid chromatography-tandem mass spectrometry (ILM) assay that simultaneously quantifies single peptides derived from HIV-1 p24 and Mycobacterium tuberculosis (Mtb) 10-kDa culture filtrate protein (CFP10) in trypsin-digested serum derived from cryopreserved serum archives of cohorts of adults and children with/without HIV and TB.<h4>Results</h4>ILM p24 and CFP10 results demonstrated good intra-laboratory precision and accuracy, with recovery values of 96.7% to 104.6% and 88.2% to 111.0%, total within-laboratory precision (CV) values of 5.68% to 13.25% and 10.36% to 14.92%, and good linearity (r2 > 0.99) from 1.0 to 256.0 pmol/L and 0.016 to 16.000 pmol/L, respectively. In cohorts of adults (n = 34) and children (n = 17) with HIV and/or TB, ILM detected p24 and CFP10 demonstrated 85.7% to 88.9% and 88.9% to 100.0% diagnostic sensitivity for HIV-1 and TB, with 100% specificity for both, and detected HIV-1 infection earlier than 3 commercial p24 antigen/antibody immunoassays. Finally, p24 and CFP10 values measured in longitudinal serum samples from children with HIV-1 and TB distinguished individuals who responded to TB treatment from those who failed to respond or were untreated, and who developed TB immune reconstitution inflammatory syndrome.<h4>Conclusions</h4>Simultaneous ILM evaluation of p24 and CFP10 results may allow for early TB and HIV detection and provide valuable information on treatment response to facilitate integration of TB and HIV diagnosis and management.Sensitive Blood-Based Detection of HIV-1 and Mycobacterium tuberculosis Peptides for Disease Diagnosis by Immuno-Affinity Liquid Chromatography-Tandem Mass Spectrometry: A Method Development and Proof-of-Concept Study.Li Lin L, Lyon Christopher J CJ, LaCourse Sylvia M SM, Zheng Wenshu W, Stern Joshua J, Escudero Jaclyn N JN, Murithi Wilfred Bundi WB, Njagi Lilian L, John-Stewart Grace G, Hawn Thomas R TR, Nduba Videlis V, Abdelgaliel Wael W, Tombler Thomas T, Horne David D, Jiang Li L, Hu Tony Y TYliquid chromatography tandem mass spectroscopy, l(3)04026, AI894280, Cyclin-dependent kinase inhibitor 1A (P21, Virulence, 1110014C03Rik, DmelCG7917, NCK5A, determination, pp21, Proheads, 21 kDa polypeptide, l(2)06 496, protein, DmelCG9893, Cahp, Human Immunodeficiency Virus 1, p35nck5a, Histamine-releasing factor, Long Term, Polypeptides, CYPIIB20, p24/p24beta1, peptido, diseases, Human Immunodeficiency Virus Type 1, Ptges, p25-alpha, Capsids, CAPG2, diseases and disorders, MAP1C, HIV-1 seropositive, protein aggregate, Effect, Tau protein kinase II 23 kDa subunit, S31I125, DNCH1, treatment, human disease, CG10733, Alpha(B)-crystallin, LCMSMS, peptides, 5830426I05Rik, MRP-1, cPGES, P21 protein, DNCL, Melanoma differentiation-associated protein 6, TEBP, p21WAF, D4S234, Pathogenicity Factors, Swl, scientific observation, p16Xic2, REA, DYHC, Therapies, Fortilin, p02, Homo sapiens disease, VMP, D4S234E, Long-Term Effects, PGs5, HRF, RNP24, LC-MS2, Therapy, cip1, CG9893, Chp, CHP, P21, CRP1, P23, LC-MS/MS, P22, Longterm Effect, P24, p24 family protein beta-1, 5H9 antigen, Virulence Factor, Cytochrome P450 2B20, dNLP-S, Cell growth-inhibiting gene 2 protein, tspan-29, p21, Diseases, Pathogenicity, Crp1, p23, p22, p25, p24, Leukocyte antigen MIC3, Calcineurin B-like protein, Tebp, hCAP-G2, Dnchc1, CG7917, SLC9A1BP, CAP20, p26/p24gamma4, CD9 antigen, CYPIIB10, Factors, MIC3, emp24, TPPP|p25, CAP-G2, Tmp-21-I, general secretion pathway-associated complex, Cdkn1, p35, Cyclin-dependent kinase 5 regulatory subunit 1, CIP1, Sid470p, Waf1, Treatments, CDK5 activator 1, WAF1, Crya2, Type 1, disease, Melanoma differentiation-associated protein, liquid chromatography-tandem mass spectroscopy, MDA-6, TPPP1, Polypeptide, AI046351, Sid 470, BCAP37, Tubulin polyglutamylase complex subunit 5, BC011290, CDKN1, other disease, p24beta1, Effects, GIG2, TCTP, Kras2, Luzp5, DHC1a, Human immunodeficiency virus 1, Gene, motility-related protein, Emp24, 5730442A20Rik, vac, CG1967, protein-containing complex, tetraspanin-29, LC-MS-MS, Loa, Human, Tspan-29, Sec-dependent secretion system-associated complex, LOJ, Dynactin complex subunit 22 kDa subunit, p21CIP1, p21Cip1, Prohead, LC-MSMS, Immunodeficiency Virus Type 1, Pathogenicity Factor, Gene Products, disease or disorder, anon-EST:Liang-1.45, Calcium-binding protein p22, SDI1, dNLP, DNECL, clone 1.45, S31III125, Longterm, CG3564, DmelCG10733, Dnecl, Long-Term, Calcium-binding protein CHP, TPPP, CDKI, non-neoplastic, 9930018I23Rik, mCAP-G2, NEEP21, 21 kDa transmembrane-trafficking protein, Crya-2, main terminal branch, disorder, peptidos, Long-Term Effect, TPPP/p25, Transmembrane protein Tmp21, MTB, Mtb, Cytochrome P450 clone PF3|46, CDK-interacting protein 1, Tetraspanin-29, Procapsid, cell growth-inhibiting gene 2 protein, measuring, Human Immunodeficiency Virus, AA960066, whole blood, 1500003O03Rik, HL-3, protein complex, Proteins, disorders, inner limiting membranes, Factor, CDK5R, Trt, medical condition, Dnec1, c-Ki-ras, Peptide, Cyclin-dependent kinase 5 activator 1, p24delta, T2SS-associated complexes, Cip1), Tmp21, LC/MS/MS, disease management., mKIAA0325, native protein, EF-hand calcium-binding domain-containing protein p22, DmelCG1967, leukocyte antigen MIC3, chemical analysis, Protein, Long Term Effects, 1.14.14.1, condition, p24.1, HspB5, p24 family protein delta-1, TPKII regulatory subunit, Protein Cdkn1a, p24delta1, sid3177, LUZP5, PNAS-141, P24A, DHC1, 0610011M09Rik, TSPAN29, Testosterone 16-alpha hydroxylase, SIIR, Bap37, Longterm Effects, Protein Gene Products, Gene Proteins, CDK5P35, 25 kDa brain-specific protein, Motility-related protein, DmelCG3564, HIV-I, Therapeutic, Cytochrome P450-16-alpha, BAP, liquid chromatography tandem mass spectrometry, Peptid, Treatment, Procapsids, Membrane protein p24A, assay, CD9, p25alpha, mda6liquid chromatography tandem mass spectroscopy, LC-MS2, Antemortem Diagnoses, screening, other disease, Antemortem Diagnosis, findings, Mycobacterium tuberculosis (Zopf 1883) Lehmann and Neumann 1896 (Approved Lists 1980), whole blood, Procedures, single-organism developmental process, postnatal development, disorders, LC-MS/MS, Human immunodeficiency virus 1, growth and development, medical condition, Procedure, Diagnosis, Peptide, Examination and Diagnoses, Diagnoses, LC-MS-MS, Human, development, Polypeptides, method, Techniques, LC/MS/MS, Postmortem, Screenings, peptido, diseases, Human Immunodeficiency Virus Type 1, sensitive, Mass Screenings, Method, Mycobacterium tuberculosis var. hominis, Examinations and Diagnoses, method used in an experiment, Immunodeficiency Virus Type 1, LC-MSMS, Diseases, Mass, symptoms, Studies, disease or disorder, Screening, condition, diseases and disorders, Antemortem, Postmortem Diagnosis, sensitivity, Technique, Bacillus tuberculosis, Diagnoses and Examination, Bacterium tuberculosis, Postmortem Diagnoses, human disease, LCMSMS, peptides, Mycobacterium tuberculosis H37Rv, postnatal growth, signs, study., Methodological, Diagnoses and Examinations, Methodological Study, non-neoplastic, plan specification, allergic reaction, Study, disease, HIV-I, Methodological Studies, liquid chromatography-tandem mass spectroscopy, disorder, liquid chromatography tandem mass spectrometry, Peptid, peptidos, Homo sapiens disease, Polypeptide, growth, Diagnose, Mycobacterium tuberculosis typus humanusliquid chromatography tandem mass spectroscopy, LC-MS2, Antemortem Diagnoses, screening, Antemortem Diagnosis, findings, Mycobacterium tuberculosis (Zopf 1883) Lehmann and Neumann 1896 (Approved Lists 1980), whole blood, LC-MS/MS, Human immunodeficiency virus 1, Diagnosis, Peptide, Examination and Diagnoses, Diagnoses, Human, Polypeptides, LC/MS/MS, Postmortem, Screenings, peptido, Human Immunodeficiency Virus Type 1, sensitive, Mass Screenings, Mycobacterium tuberculosis var. hominis, Examinations and Diagnoses, Immunodeficiency Virus Type 1, LC-MSMS, Mass, symptoms, Screening, Antemortem, Postmortem Diagnosis, sensitivity, Bacillus tuberculosis, Diagnoses and Examination, Bacterium tuberculosis, Postmortem Diagnoses, LCMSMS, peptides, Mycobacterium tuberculosis H37Rv, signs, Diagnoses and Examinations, allergic reaction, HIV-I, liquid chromatography-tandem mass spectroscopy, liquid chromatography tandem mass spectrometry, Peptid, peptidos, LC-MS-MS., Polypeptide, Diagnose, Mycobacterium tuberculosis typus humanusliquid chromatography tandem mass spectroscopy, l(3)04026, AI894280, Archive, Human T-Cell Lymphotropic Virus Type III, Cyclin-dependent kinase inhibitor 1A (P21, 1110014C03Rik, Antemortem Diagnosis, DmelCG7917, NCK5A, determination, pp21, Laboratory, Blood, 21 kDa polypeptide, AIDS Virus, l(2)06 496, protein, B-cell receptor complex, DmelCG9893, Cahp, Serum, Diagnosis, Human Immunodeficiency Virus 1, Human Immunodeficiency, p35nck5a, Histamine-releasing factor, Lymphadenopathy Associated Virus, Polypeptides, Techniques, CYPIIB20, p24/p24beta1, peptido, Human Immunodeficiency Virus Type 1, Method, Ptges, p25-alpha, Mycobacterium tuberculosis var. hominis, Virus, Antigen, symptoms, CAPG2, MAP1C, HIV-1 seropositive, protein aggregate, Fs(3)Hor, Immune Restoration Disease, Human immunodeficiency virus, Tau protein kinase II 23 kDa subunit, S31I125, adult, DNCH1, treatment, Bacillus tuberculosis, Bacterium tuberculosis, DmelCG2684, CG10733, Alpha(B)-crystallin, LCMSMS, peptides, kDa, MRP-1, 5830426I05Rik, membrane bound, cPGES, P21 protein, DNCL, procedures, Melanoma differentiation-associated protein 6, TEBP, NTef2, p21WAF, D4S234, allergic reaction, Immune, Methodological Studies, Swl, scientific observation, p16Xic2, TB, disease management, REA, Therapies, DYHC, Fortilin, p02, VMP, B-lymphocyte receptor complex, D4S234E, PGs5, HRF, Immune Restoration Syndrome, Diagnose, RNP24, LC-MS2, close to, Therapy, screening, Mycobacterium tuberculosis (Zopf 1883) Lehmann and Neumann 1896 (Approved Lists 1980), cip1, CG9893, Chp, CHP, P21, CRP1, P23, LC-MS/MS, P22, P24, Procedure, Blood Serum, p24 family protein beta-1, antibodies, 5H9 antigen, results, Fs(3)Sz11, Diagnoses, Cytochrome P450 2B20, dNLP-S, Postmortem, Screenings, AIDS, Cell growth-inhibiting gene 2 protein, tspan-29, Examinations and Diagnoses, p21, Crp1, p23, p22, p25, p24, Leukocyte antigen MIC3, laboratory, Calcineurin B-like protein, Tebp, Postmortem Diagnosis, Early, Adults, Dnchc1, CG7917, hCAP-G2, SLC9A1BP, CAP20, p26/p24gamma4, Acquired Immune Deficiency Syndrome Virus, Diagnoses and Examination, CD9 antigen, CYPIIB10, Postmortem Diagnoses, Lymphadenopathy-Associated, MIC3, emp24, TPPP|p25, Tmp-21-I, CAP-G2, general secretion pathway-associated complex, Cdkn1, p35, signs, Cyclin-dependent kinase 5 regulatory subunit 1, Methodological, CIP1, Sid470p, Methodological Study, beta Trypsin, Children, Treatments, Waf1, CDK5 activator 1, WAF1, Crya2, early, Type 1, immunoglobulin, B cell receptor accessory molecule complex, Melanoma differentiation-associated protein, Patient, Specificity and Sensitivity, liquid chromatography-tandem mass spectroscopy, Horka, Acquired Immunodeficiency Syndrome Virus, B lymphocyte receptor complex, MDA-6, TPPP1, CG2684, Fs(3)Horka, Polypeptide, AI046351, Diagnoses., Sid 470, BCAP37, Tubulin polyglutamylase complex subunit 5, BC011290, active tuberculosis, Restoration Syndrome, CDKN1, human immunodeficiency virus infectious disease, Disease Early Detection, p24beta1, Procedures, GIG2, TCTP, Kras2, DHC1a, Luzp5, Human immunodeficiency virus 1, HTLV-III, motility-related protein, Gene, Emp24, 5730442A20Rik, Immune Reconstitution Syndrome, vac, CG1967, protein-containing complex, tetraspanin-29, LC-MS-MS, Loa, Human, Tspan-29, antibody, Sec-dependent secretion system-associated complex, culture filtrate, LOJ, Dynactin complex subunit 22 kDa subunit, BCR complex, p21CIP1, p21Cip1, sensitive, Immunodeficiency Virus Type 1, LC-MSMS, Studies, Gene Products, Mass, Immune Restoration Diseases, Screening, Kochs disease, DmF2, Human T-Cell Leukemia Virus Type III, anon-EST:Liang-1.45, Antemortem, immunoglobulin complex, Technique, sensitivity, Calcium-binding protein p22, SDI1, dNLP, lod, Human T-Lymphotropic Virus Type III, DNECL, Viruses, clone 1.45, S31III125, CG3564, beta-Trypsin, DmelCG10733, Immunodeficiency Viruses, Dnecl, Diagnoses and Examinations, Human T Cell Leukemia Virus Type III, Calcium-binding protein CHP, TPPP, CDKI, Study, 9930018I23Rik, NEEP21, mCAP-G2, Clients, 21 kDa transmembrane-trafficking protein, Reconstitution Syndrome, Crya-2, Lymphadenopathy-Associated Viruses, main terminal branch, Sensitivity, peptidos, HIV, TPPP/p25, Human Immunodeficiency Viruses, Transmembrane protein Tmp21, MTB, Mtb, Cytochrome P450 clone PF3|46, CDK-interacting protein 1, Tetraspanin-29, Lymphadenopathy-Associated Virus, cell growth-inhibiting gene 2 protein, measuring, Antemortem Diagnoses, Human Immunodeficiency Virus, Human T Lymphotropic Virus Type III, culture medium, findings, AA960066, 1500003O03Rik, HL-3, Immune Reconstitution Syndromes, protein complex, Proteins, inner limiting membranes, CDK5R, Trt, Dnec1, c-Ki-ras, Client, Peptide, Examination and Diagnoses, Cyclin-dependent kinase 5 activator 1, near to, p24delta, Early Detection of Disease, T2SS-associated complexes, Cip1), Tmp21, LC/MS/MS, mKIAA0325, native protein, Immunodeficiency Virus, EF-hand calcium-binding domain-containing protein p22, Mass Screenings, DmelCG1967, leukocyte antigen MIC3, chemical analysis, Protein, 1.14.14.1, Reconstitution Disease, p24.1, HspB5, background, techniques, p24 family protein delta-1, TPKII regulatory subunit, Protein Cdkn1a, AIDS virus, p24delta1, sid3177, LUZP5, opsonin activity, PNAS-141, PRSS, AIDS Viruses, P24A, DHC1, Mycobacterium tuberculosis H37Rv, culture supernatant, 0610011M09Rik, Tripcellim, Specificity, patient, TSPAN29, Testosterone 16-alpha hydroxylase, SIIR, Bap37, Lds, LAV-HTLV-III, introduction, Protein Gene Products, CDK5P35, Gene Proteins, Trypure, 25 kDa brain-specific protein, Motility-related protein, DmelCG3564, HIV-I, Therapeutic, approaches, vicinity of, Cytochrome P450-16-alpha, B cell receptor activity, BAP, Immune Reconstitution Disease, liquid chromatography tandem mass spectrometry, Treatment, Peptid, Membrane protein p24A, assay, CD9, Human T Cell Lymphotropic Virus Type III, Serums, methodology, p25alpha, Mycobacterium tuberculosis typus humanus, mda60falseSensitive detection of HIV-1 and Mycobacterium tuberculosis peptides in blood for rapid diagnosis of co-infected individuals by immuno-affinity liquid chromatography tandem mass spectrometryWe describe a blood-based immuno-affinity liquid chromatography tandem mass spectrometry (ILM) assay that quantifies proteotypic peptides derived from the Mtb virulence factor CFP10 and the HIV-1 capsid protein p24 to simultaneously diagnose HIV-1 infection and TB disease and to monitor their real-time response to treatment.Wed Nov 15 00:00:00 GMT 2023PXD043191960637956323