Selective capture of anti‐N‐glucosylated NTHi adhesin peptide antibodies by a multivalent dextran conjugate

Background:Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific and sensitive markers for rheumatoid arthritis (RA). There are also suggested to have a more severe rheumatoid arthritis.Objectives:The aim of this study was to assess the influence of ACPA on disease activity, radiological severity, and functional disability in Algerian patient with early rheumatoid arthritis (RA).Methods:Consecutive early RA patients (symptom duration ≤24 months) recruited were included in the descriptive, longitudinal, prospective study. Demographic, biological, immunological and radiographic data were collected at the time of inclusion in the study. Disease activity as determined by the Disease Activity Score 28-CPR (DAS28- CPR: 4 variables), functional handicap as calculated by Heath Assessment Score (HAQ), and bone and joint damage as evaluated by Sharp-Van der Heijde (SVDH) erosion and narrowing score.Results:One hundred and sixty-one patients with RA were recruited. Patients mean age 43.71±14 years and mean symptom duration at inclusion was 10.48±7 months. Small and larges were affected in 64,3%. The mean ESR was 23,53±15,2 mm/1st hour, and the mean CRP level was 19,42±39.8 mg/l. Rheumatoid Factors (RFs) and Anti-Citrullinated Protein Antibodies (ACPAs) were present in 74% and 88% of patients, respectively. The presence of ACPAs was significantly associated with DAS28 (p=0,004) and HAQ (p=0,002). There was no significant difference in inflammatory markers and radiographic SVDH score between patients with and without ACPAs. Stepwise regression analysis showed that the presence of ACPAs was independently associated with localization when RA affected smalls and larges joint in the same time (OR=5,24; IC 95% 1,224-22,483; p=0,026).Conclusion:These data show that in patients with early RA, ACPAs positivity was significantly associated with articular manifestations, activity disease and functional handicap, but not with structural damage.References:[1]Nikiphorou E, Norton S, Young A, et al. Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery: combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds. Ann Rheum Dis. 2016;75(12):2080-2086. doi:10.1136/annrheumdis-2015-208669.[2]Karimifar M, Salesi M, Farajzadegan Z. The association of anti-CCP1 antibodies with disease activity score 28 (DAS-28) in rheumatoid arthritis. Adv Biomed Res. 2012;1:30. doi:10.4103/2277-9175.98156.[3]Boman A, Brink M, Lundquist A, et al. Antibodies against citrullinated peptides are associated with clinical and radiological outcomes in patients with early rheumatoid arthritis: a prospective longitudinal inception cohort study. RMD Open. 2019;5(2):e000946. Published 2019 Sep 3. doi:10.1136/rmdopen-2019-000946.Disclosure of Interests:None declared

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Development of a Macromolecular Prodrug of FK 506: III: In Vivo Disposition of FK 506-Dextran Conjugate

Transplantation Proceedings ◽

10.1016/s0041-1345(98)00137-7 ◽

1998 ◽

Vol 30 (4) ◽

pp. 1029-1030 ◽

Cited By ~ 1

Author(s):

N Yoshimura ◽

H Yura ◽

T Hamashima ◽

T Oka ◽

Y Takakura ◽

...

Keyword(s):

Fk 506 ◽

Macromolecular Prodrug ◽

Dextran Conjugate

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Identification of a functionally conserved surface region of rat cytochromes P450IA

Biochemical Journal ◽

10.1042/bj2780749 ◽

1991 ◽

Vol 278 (3) ◽

pp. 749-757 ◽

Cited By ~ 19

Author(s):

R J Edwards ◽

A M Singleton ◽

B P Murray ◽

S Murray ◽

A R Boobis ◽

...

Keyword(s):

Affinity Purification ◽

Cytochromes P450 ◽

Surface Region ◽

Carrier Protein ◽

Peptide Antigen ◽

Aryl Hydrocarbon ◽

C Terminus ◽

Aryl Hydrocarbon Hydroxylase Activity ◽

The Difference ◽

Peptide Antibodies

A region of rat cytochrome P450IA1 at residues 294-301 (Gln-Asp-Arg-Arg-Leu-Asp-Glu-Asn), equivalent to a proinhibitory region of cytochrome P450IA2, was identified by sequence alignment. Anti-peptide antibodies were successfully raised when the peptide was coupled through either its N- or its C-terminus to carrier protein, but no antibodies were produced against the so-called multiple peptide antigen, which consisted of eight copies of the peptide attached through its C-terminus to a synthetic base. Both of the anti-peptide antibodies bound specifically to cytochrome P450IA1 in the rat, as shown by e.l.i.s.a. and immunoblotting. They inhibited microsomal aryl hydrocarbon hydroxylase activity and the mutagenic activation of 2-acetylaminofluorene (these reactions are catalysed by cytochrome P450IA1), but not high-affinity phenacetin O-de-ethylation activity, which is catalysed by cytochrome P450IA2. However, there was differences in the properties of the two antisera in their binding to cytochromes P450IA1 in species other than the rat, their relative binding to the multiple peptide antigen, the yield of antibody following affinity purification using peptide coupled through its N-terminus to CNBr-activated Sepharose, and the binding of the purified preparations to N- and C-terminal-coupled peptide conjugates. These observations indicated that the antibodies were directed to the region of the peptide opposite to the end which was coupled to the carrier protein. Nevertheless, both of the antibody preparations bound equally well to the target cytochrome P450, thus indicating that, in the native protein, the whole of the peptide region is exposed on the surface of cytochrome P450IA1 and is available for binding by the antibodies. The role of this region appears to be the same in both cytochromes P450IA1 and P450IA2, despite the difference in its primary structure in the two cytochromes P450.

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Circulating anti-citrullinated peptide antibodies, cytokines and genotype as biomarkers of response to disease-modifying antirheumatic drug therapy in early rheumatoid arthritis

BMC Musculoskeletal Disorders ◽

10.1186/s12891-015-0587-1 ◽

2015 ◽

Vol 16 (1) ◽

Cited By ~ 20

Author(s):

Mahmood M. T. M. Ally ◽

Bridget Hodkinson ◽

Pieter W. A. Meyer ◽

Eustasius Musenge ◽

Gregory R. Tintinger ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Drug Therapy ◽

Early Rheumatoid Arthritis ◽

Antirheumatic Drug ◽

Disease Modifying ◽

Antirheumatic Drug Therapy ◽

Citrullinated Peptide ◽

Disease Modifying Antirheumatic Drug ◽

Peptide Antibodies

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Urinary excretion characteristics of a polymeric prodrug of mitomycin C, mitomycin C-dextran conjugate.

Journal of Pharmacobio-Dynamics ◽

10.1248/bpb1978.8.357 ◽

1985 ◽

Vol 8 (5) ◽

pp. 357-364 ◽

Cited By ~ 16

Author(s):

YOSHINOBU TAKAKURA ◽

AKIRA KATO ◽

MITSURU HASHIDA ◽

KAZUO HONDA ◽

AKIRA ARIMOTO ◽

...

Keyword(s):

Urinary Excretion ◽

Mitomycin C ◽

Polymeric Prodrug ◽

Dextran Conjugate

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Markers of the early stage of rheumatoid arthritis

Diagnostyka Laboratoryjna ◽

10.5604/01.3001.0008.2523 ◽

2016 ◽

Vol 51 (4) ◽

pp. 305-314

Author(s):

Beata Polińska ◽

Joanna Matowicka-Karna ◽

Halina Kemona

Keyword(s):

Rheumatoid Arthritis ◽

Human Population ◽

Early Stage ◽

Clinical Signs ◽

High Sensitivity ◽

Unknown Etiology ◽

Serological Tests ◽

Citrullinated Peptide ◽

Peptide Antibodies

Rheumatoid arthritis (RA) is a chronic, autoimmune connective tissue disease of unknown etiology. RA affects about 1% of the human population, women suffer three times more often than men, with the peak incidence between the age of 40 to 50. The up-to-date criteria from 2010 for the diagnosis of RA include: occurrence and duration of clinical signs, indicators of inflammation and serological tests. Neopterin, a protein released by macrophages, is a sensitive indicator of inflammation and the severity of RA. Regarding the serological tests, anti-cyclic citrullinated peptide antibodies represent a well-known marker with the specificity for RA of about 98%. The antibodies may be present in the serum of patients even a few years before the first clinical signs of the disease, heralding erosive changes in the joints and more severe course of RA. The literature also contains reports about autoantibodies anti-CarP and anti-Sa/ anti-MCV, which may occur in people with pain and swelling of joints and precede full-blown development of RA as well as reflect disease activity. Serological diagnosis of RA may be supported by some genetic tests based on PCR for detecting mutations e.g. C1858T in the PNPN22 gene. In turn, the quantitative analysis of different classes of miRNAs seems justified in order to better classify patients showing symptoms of RA. Further studies are needed that take into account the role of different markers in the development of RA, and confirm the high sensitivity and specificity of these markers in the diagnosis of the disease.

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