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Serum and urine galactose deficient-IgA1 as alternative biomarkers in the management of IgA nephropathy

Suleman AA, Abd Ghani F, Fadhlina NZ, Rafidah H

Med J Malaysia, 2024 Jan;79(1):95-101.
PMID: 38287764

INTRODUCTION: Immunoglobulin A (IgA) nephropathy (IgAN) results from abnormal accumulation of immune complexes containing galactose deficient IgA1 (Gd-IgA1) in the kidneys. About 40% of patients develop end-stage kidney disease within 20 years of renal biopsy. At present, the diagnosis and risk stratification of patients (using the international IgAN risk prediction tool) rely on renal biopsy, which is an invasive procedure. Also, treatment decisions are still dependent on proteinuria, which is not specific for IgA nephropathy. We discussed the role of serum and urine Gd- IgA1 in the diagnosis of IgAN, its association with disease progression and changes with treatment in patients with IgA nephropathy.
MATERIALS AND METHODS: A systematic search of PubMed and Scopus databases was done to identify the articles that are relevant to the topic including systematic reviews and original articles.
RESULTS: Several studies showed that both serum and urine Gd-IgA1 differentiate IgA nephropathy patients from healthy people and other glomerulonephropathies. Thus, it is useful as a less invasive diagnostic biomarker, although detection methods varied between studies with different sensitivities. There are various reports of its use as a prognostic parameter. Evidence is emerging for its use as a monitoring parameter for treatment.
CONCLUSION: Galactose deficient IgA1 is a promising biomarker in the management of IgA nephropathy, although a more robust and standardised means of estimation is required.

Matched MeSH terms: Immunoglobulin A
Low incidence of selective IgA deficiency in normal Malaysians

Yadav M, Iyngkaran N

Med J Malaysia, 1979 Dec;34(2):145-8.
PMID: 548716
Matched MeSH terms: Immunoglobulin A/analysis
Fulltext Histopathological Study of the Lungs of Mice Receiving Human Secretory IgA and Challenged with Mycobacterium tuberculosis

Alvarez N, Infante JF, Borrero R, Mata D, Payan JB, Hossain MM, et al.

Malays J Med Sci, 2014 May;21(3):31-7.
PMID: 25246833 MyJurnal

Humoral and cellular immune responses are associated with protection against extracellular and intracellular pathogens, respectively. In the present study, we evaluated the effect of receiving human secretory immunoglobulin A (hsIgA) on the histopathology of the lungs of mice challenged with virulent Mycobacterium tuberculosis.

Matched MeSH terms: Immunoglobulin A; Immunoglobulin A, Secretory
Actions of three clostridial IgA proteases on distinct forms of immunoglobulin A molecules

Hashim OH, Hassan H

Immunology, 1991 Jun;73(2):235-8.
PMID: 2071167

Three bacterial species of Clostridium (septicum, tertium and sporogenes) were identified to produce extracellular proteases cleaving IgA to Fab and Fc fragments, as demonstrated by SDS-PAGE and immunoelectrophoretic procedures. These enzymes acted on monometric IgA1 paraproteins and normal serum IgA1 but had no activity on IgA2 paraproteins and intact secretory IgA1 from human colostrum. Their action on polyclonal serum IgA1 suggested the absence of neutralizing anti-clostridial IgA protease activity. Although the enzymes were shown not to act on secretory IgA1, they were, however, able to digest free alpha-heavy chains of the dimeric IgA molecules. Susceptibility of the alpha-heavy chain to the proteases was more likely due to the change to a more accessible conformation than because of the absence of neutralizing anti-enzymic activity.

Matched MeSH terms: Immunoglobulin A/metabolism*; Immunoglobulin A, Secretory/metabolism
Fulltext A rare occurrence of plasma cell myeloma with biclonal gammopathy

Mardziah, M., Nurasyikin, Y., Rafeah, T., Dian, N., Yousuf, R., Suria, A.A.

Medicine & Health, 2017;12(1):103-108.
MyJurnal

Plasma cell myeloma is known to cause expansion of a single clone of munoglobulin (Ig) which results in the secretion of a unique homogeneous monoclonal protein (M component). However, there are cases which reported that it can also cause production of two different clones of these monoclonal proteins. Although it is relatively very rare as the prevalence is only 2% of all plasma cell myeloma cases, the clinical features are said to be similar to monoclonal gammopathy. It is suggested that these biclonal gammopathy results from either one monoclonal cell clone in monoclonal gammopathy or two different monoclonal cell clones. Whichever the mechanism of the disease be, the response to treatment seems to be similar as compared to the monoclonal cases although some reports shows chemoresistant. Here, we report a rare case of plasma cell myeloma with IgG (lambda) and IgA (lambda) type of biclonal gammopathy, the clinical presentation, the haematological and biochemical markers as well as the response to the treatment.
Keywords: biclonal gammopathy, M protein, plasma cell myeloma

Matched MeSH terms: Immunoglobulin A
Fulltext Changes in salivary immunoglobulin A (IgA) following match-play and training among English premiership footballers

Fredericks S, Fitzgerald L, Shaw G, Holt DW

Med J Malaysia, 2012 Apr;67(2):155-8.
PMID: 22822634

Decreased salivary immunoglobulin A (sIgA), a component of mucosal immunity, is associated with intensive physical activity: suggesting that sIgA may be used for the monitoring of mucosal immunity with footballers. We investigated changes in sIgA in elite footballers, in response to training and match-play. There was a decrease in sIgA following training, with a return to pre-training levels after 18 hours of rest. This return to resting levels was not observed following competitive match-play. Overnight rest was sufficient for mucosal IgA recovery following training but not following two successive matches, suggesting that sIgA may be used to monitor training in multi-sprint sports.

Matched MeSH terms: Immunoglobulin A/immunology*
Comparative analyses of IgA1 binding lectins from seeds of six distinct clones of Artocarpus integer

Hashim OH, Gendeh GS, Jaafar MI

Biochem. Mol. Biol. Int., 1993 Jan;29(1):69-76.
PMID: 8490570

Purified lectins from seeds of six distinct clones of Artocarpus integer (lectin C) were shown to be structurally and functionally similar. All lectins comprised of two types of non-covalently-linked subunits with apparent M(r) of 13,300 and 16,000. The lectins appeared to interact with several human serum proteins, with the predominance of the IgA1 and C1 inhibitor molecules. Interaction was not detected with IgA2, IgD, IgG and IgM. The lectin Cs were also shown to precipitate monkey, sheep, rabbit, cat, hamster, rat and guinea-pig serum. Due to their uniform properties, lectin C may provide better alternative to the Artocarpus heterophyllus lectin, jacalin, for use in future investigations.

Matched MeSH terms: Immunoglobulin A/metabolism*
Fulltext Aids to diagnosis of nasopharyngeal carcinoma

Umapati P, Rajadurai P, Kook SC, Lekhraj R, Singh J

Med J Malaysia, 1988 Jun;43(2):109-16.
PMID: 3237126
Matched MeSH terms: Immunoglobulin A/analysis
Fulltext Comparative evaluation of salivary immunoglobulin a levels between pedodontic subjects

Jha A, Singh R, Jha S, Singh S, Chawla R, Prakash A

J Family Med Prim Care, 2020 Apr;9(4):2052-2055.
PMID: 32670964 DOI: 10.4103/jfmpc.jfmpc_967_19

Background and Aims: Host immune response is altered by a series of physiologic and pathologic factors like age, gender, inflammation, surgery, medication etc., The present study was conducted to evaluate differences in salivary IgA (S-IgA) levels among pedodontic subjects undergoing active orthodontic treatment with fixed and removable appliance. The levels of S- IgA were determined before 3 months and 6 months post active orthodontic treatment.
Methods: A total of 40 healthy pedodontic subjects (aged 8-15 years) were recruited in the present study. They were equally divided into Group A (fixed orthodontic group) and Group B (removable orthodontic group) with 20 subjects each. 1.5 mL of saliva per subject was obtained before 3 and 6 months after treatment. Enzyme Linked Immunosorbent Assay (ELISA) technique was used for measurement of Salivary IgA levels.
Results: Group A and B both showed significant rise in S-IgA levels 3 months and 6 months post active orthodontic treatment. Mean value of S-IgA 3 months post treatment in the saliva of children in group B and group A were (144.27 ± 5.32) and (164.0 ± 3.23) μg/ml respectively. While mean value of S-IgA after 6 months of treatment in group B and group A were (149.8 ± 6.02) and (166.4 ± 3.65) μg/ml respectively.
Conclusion: Salivary Immunoglobulin A level values were significantly higher statistically in both group A and group B post active orthodontic treatment than before. The results however, showed that Group A (fixed orthodontic group) showed statistically significant higher levels of S-IgA than Group B (removable orthodontic group). Active orthodontic treatment triggered a stronger stimulus for oral secretory immunity, hence the increase in levels were detected. There is a significant positive correlation between S-IgA and active fixed as well as removable orthodontic treatment. Orthodontic treatment is hence a local immunogenic factor.

Matched MeSH terms: Immunoglobulin A; Immunoglobulin A, Secretory
Normal plasma-immunoglobulin levels in Malaysians

Yadav M, Shah FH

Lancet, 1973 Aug 25;2(7826):450-1.
PMID: 4124938
Matched MeSH terms: Immunoglobulin A/analysis
Normal serum immunoglobulin G, A and M levels in full term Malaysian newborns

Yadav M, Shah FH

Med J Malaysia, 1979 Mar;33(3):247-51.
PMID: 522730
Matched MeSH terms: Immunoglobulin A/analysis*
Serum immunoglobin A. G and M levels in blood donors of four racial groups in Malaysia

Yadav M, Shah FH

Trop Geogr Med, 1977 Sep;29(3):245-50.
PMID: 595130

Serum levels were determined in urban Chinese, Malays and Indians and in the forest-residing Orang Asli of age group 11 to 50. There was no difference in the IgM levels in the Chinese, Indians and Malays, but the serum IgG was elevated (p less than 0.05) in the Malays and the serum IgA level (p less than 0.01) in the Indians, when compared to the other two races. In contrast to the three other races there was a significant elevation of all three immunoglobulins in the Orang Asli. The mean immunoglobulin levels of the urban Malaysians are comparable to those reported for Caucasians residing in temperate countries. However, in the Orang Asli, the immunoglobulin levels were higher than observed for populations of the temperate regions but are comparable to the levels reported for several other populations of the tropical regions. Females had higher IgM levels than males in the Chinese, Indian and Malays but in the Orang Asli there was no sex difference in the immunoglobulin levels.

Matched MeSH terms: Immunoglobulin A*; Immunoglobulin G*; Immunoglobulin M*
Immunological studies in Malaysian patients with rheumatoid arthritis

Sivapatham G, Gong NC, Pang T

ASEAN Journal of Clinical Sciences, 1982;3(4):329-33.

Twenty-one patients with rheumatoid arthritis (RA) were investigated for various immunological parameters, both humoral and cellular. IgG concentration was 1673+/-266 mg/dl, IgM 259+/-108 mg/dl and IgA 302 +/-7 mg/dl. Enumeration of T lymphocytes in peripheral blood revealed a value of 66% with a B cell count of 10%. Additionally, IgG levels, in 5 selected patients, appeared to fall to normal levels in the course of treatament with D-penicillamine. The significance of these findings are discussed.

Matched MeSH terms: Immunoglobulin A
Generation of a T cell receptor (TCR)-like single domain antibody (sDAb) against a Mycobacterium Tuberculosis (Mtb) heat shock protein (HSP) 16kDa antigen presented by Human Leukocyte Antigen (HLA)-A*02

Dass SA, Norazmi MN, Dominguez AA, Miguel MESGS, Tye GJ

Mol Immunol, 2018 09;101:189-196.
PMID: 30007228 DOI: 10.1016/j.molimm.2018.07.001

The discovery of heat shock protein 16 kDa antigen protein has deepen the understanding of latent tuberculosis since it was found to be primarily expressed by Mycobacterium tuberculosis during latent phase leading to the rapid optimization and development in terms of diagnosis and therapeutics. Recently, T cell receptor-like antibody has been explored extensively targeting various diseases due to its dual functionality (T cell receptor and antibody). In this study, a TCR-like domain antibody (A2/Ab) with the binding capacity to Mtb heat shock protein (HSP) 16 kDa antigen presented by major histocompatible complex (MHC) HLA-A*02 was successfully generated via biopanning against human domain antibody library. The generated antibody (A2/Ab) exhibited strong functionality and binding capacity against the target assuring the findings of this study to be beneficial for the development of latent tuberculosis diagnosis and immunotherapeutics in future.

Matched MeSH terms: Immunoglobulin A
Identification and characterization of human serum alpha2-HS glycoprotein as a jacalin-bound protein

To WY, Leung JC, Lai KN

Biochim. Biophys. Acta, 1995 May 18;1249(1):58-64.
PMID: 7766684

We recently adopted immobilized jacalin as an affinity adsorbent to purify human serum IgA for laboratory study. In the course of our investigation, we detected a serum protein that co-eluted with IgA from jacalin-agarose affinity column. It constituted in significant quantity (24.0 +/- 0.9%, n = 30) of total jacalin-bound protein (JBP) and the yield was equivalent to 0.4 +/- 0.1 mg per ml serum. The molecular mass of this protein was 55 kDa with electromobility in the alpha 2 region as demonstrated by SDS-PAGE and immunoelectrophoresis. N-terminal microsequencing of this 55 kDa protein revealed that it is human alpha 2-HS glycoprotein (alpha 2HSG). The molecular interaction of alpha 2HSG with jacalin was characterized by competitive ELISA: human serum IgA, human colostrum secretory IgA (sIgA), and monosaccharides including D-galactose and melibiose exhibited strong inhibitory effect on its binding to jacalin. Accordingly, we propose that human alpha 2HSG binds in a similar manner as that of the bovine fetuin to jacalin. In addition, alpha 2HSG displays similar binding property to jacalin from different geographic area (India and Malaysia) and from different laboratory preparations (Sigma, Pierce and 'homemade' jacalin).

Matched MeSH terms: Immunoglobulin A/isolation & purification; Immunoglobulin A/chemistry
Antibody response to Helicobacter pylori excretory antigen and the cross reaction study

Sasidharan S, Uyub AM

J Immunoassay Immunochem, 2009;30(1):70-81.
PMID: 19117203 DOI: 10.1080/15321810802569477

Helicobacter pylori is recognized as a major case of gastritis and peptic ulcer and a key factor in the development of gastric cancer, gastric lymphoma, and non-ulcerative dyspepsia in man. The detection of antibodies specific for strains of H. pylori has demonstrated the value of serology for providing evidence of infection. The present study was conducted to detect the antigenic proteins of excretory antigen of H. pylori with Western blotting and examine whether anti-H. pylori IgG and IgA antibodies from H. pylori positive patients cross-react with antigens from other common bacterial pathogens. By using SDS-PAGE, 20 different proteins were found in the excretory antigen. By Western blotting and absorption studies, there were indications that anti-H. pylori IgA antibodies directed against 54 kDa, 50 kDa and 27 kDa cross-reacted with antigens from other bacteria, and that H. pylori proteins of 99 kDa, 88 kDa and 81 kDa possibly shared similar epitope with antigens of other pathogens not tested in the absorption studies. The cross-reactivity occurred in this study was not significantly affect the performance of the in-house ELISA.

Matched MeSH terms: Immunoglobulin A/blood; Immunoglobulin A/immunology
The interaction of selective plant lectins with neuraminidase-treated and untreated IgA1 from the sera of IgA nephropathy patients

Hashim OH, Shuib AS, Chua CT

Immunol Invest, 2001 Feb;30(1):21-31.
PMID: 11419909

A study on the binding interaction of lectins from Artocarpus heterophyllus (jacalin), Glycine max and Sambucus nigra with standardised quantity of IgA from the IgA nephropathy patients and normal controls was performed. The Glycine max lectin demonstrated higher affinity towards the serum IgA of IgAN patients as compared to normal controls. However, the affinity binding was lower in cases ofjacalin and the Sambucus nigra lectin. When serum samples were treated with neuraminidase, the differential jacalin affinity binding between IgA1 of patients and normal controls was abrogated. Our data are in support of the view that the O-linked oligosaccharide moieties of the patients IgA1 were generally lacking in galactose and sialic acid residues.

Matched MeSH terms: Immunoglobulin A/blood*; Immunoglobulin A/chemistry
Fulltext Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study

Fedirko V, Tran HQ, Gewirtz AT, Stepien M, Trichopoulou A, Aleksandrova K, et al.

BMC Med, 2017 04 04;15(1):72.
PMID: 28372583 DOI: 10.1186/s12916-017-0830-8

BACKGROUND: Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking.
METHODS: We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression.
RESULTS: Antibody response to LPS and flagellin was associated with a statistically significant increase in the risk of hepatocellular carcinoma (highest vs. lowest quartile: RR = 11.76, 95% confidence interval = 1.70-81.40; P trend = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses.
CONCLUSIONS: These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted.

Matched MeSH terms: Immunoglobulin A/blood*; Immunoglobulin A/immunology
Neuraminidase treatment abrogates the binding abnormality of IgA1 from IgA nephropathy patients and the differential charge distribution of its alpha-heavy chains

Hashim OH, Shuib AS, Chua CT

Nephron, 2001 Dec;89(4):422-5.
PMID: 11721160

We have studied the interaction of the Gal-GalNAc-reactive champedak lectin-C with neuraminidase-treated and untreated IgA1 from IgA nephropathy patients. The binding ability of the lectin to untreated IgA1 from IgA nephropathy patients was significantly lower as compared to the untreated IgA1 from normal controls. This differential lectin-binding capacity was abrogated when the experiment was performed on neuraminidase-treated sera. Treatment of the serum IgA1 with neuraminidase also abrogated the differential charge distribution between the alpha-heavy chains of IgA nephropathy patients and normal controls.

Matched MeSH terms: Immunoglobulin A/immunology; Immunoglobulin A/metabolism*; Immunoglobulin A/chemistry; Immunoglobulin alpha-Chains/immunology; Immunoglobulin alpha-Chains/metabolism; Immunoglobulin alpha-Chains/chemistry
Pimecrolimus 1% cream for mild-to-moderate atopic dermatitis: a systematic review and meta-analysis with a focus on children and sensitive skin areas

Luger T, Chu CY, Elgendy A, Ibrahim SBBK, Murashkin N, Ranjan S, et al.

Eur J Dermatol, 2023 Oct 01;33(5):474-486.
PMID: 38297923 DOI: 10.1684/ejd.2023.4556

This systematic literature review (SLR) and meta-analysis assessed the efficacy and safety of pimecrolimus vs other topical treatments in patients with mild-to-moderate atopic dermatitis (AD), focusing on children and sensitive skin areas. An SLR was conducted in MEDLINE, Embase and Cochrane Library databases on January 15th, 2020, to identify randomized controlled trials (RCTs) with pimecrolimus as a study arm. Another SLR performed on October 5th, 2020 identified RCTs with a crisaborole study arm. Direct pair-wise meta-analysis was used to compare pimecrolimus with vehicle, tacrolimus or topical corticosteroids (TCS; n = 27 studies). Outcomes included Investigator's Global Assessment (IGA) score 0/1 up to week 6 and adverse events. Pimecrolimus was more efficacious than vehicle in achieving IGA 0/1 up to week 6 in children, and similar safety profiles were observed with pimecrolimus and vehicle in children and the mixed population, including on sensitive skin. No significant differences in efficacy and safety were observed between pimecrolimus and tacrolimus 0.03%. Efficacy and safety were similar for pimecrolimus and mild medium potency TCS; mildly potent steroids caused transient epidermal thinning in sensitive skin areas (not seen with pimecrolimus). Pimecrolimus can be considered as a first-line option for mild-to-moderate AD, particularly in children and sensitive skin areas.

Matched MeSH terms: Immunoglobulin A

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