Nasal carriage of Staphylococcus aureus was associated with a distinct disease phenotype among patients with systemic lupus erythematosus, Italian researchers found.
At the time of enrollment into a lupus cohort, renal involvement was more common among S. aureus carriers than noncarriers (11.6% vs 3%, P=0.0009), while joint involvement was less frequent (11.1% vs 21.2%, P=0.02), according to Cristiano Alessandri, MD, of Sapienza Universita di Roma in Rome, and colleagues.
The carriers also had higher prevalence of several lupus-associated autoantibodies such as anti-double stranded (ds) DNA (77.7% vs 39.4%, P<0.0001), the researchers reported online in Arthritis Research & Therapy.
"In recent years there has been growing interest in the possible role of the microbiome in the development and course of disease. Of note, the gut microbiome has been widely investigated in autoimmune diseases, such as type 1 diabetes, inflammatory bowel diseases, rheumatoid arthritis, and spondyloarthropathies," Alessandri and colleagues wrote.
Less is known, however, about the skin microbiome, which acts as the primary barrier against pathogenic insults and, when out of balance, could be associated with disease.
The commensal S. aureus can be found intermittently in the anterior nares in approximately one-third of the population. Its presence has been associated with atopic dermatitis, and studies have considered a possible association with other skin disorders such as acne vulgaris and rosacea.
In addition, a study in patients with rheumatoid arthritis found carriage rates of 50% compared with 33% in controls, and another study found an association between carriage and disease development and relapse in granulomatosis with polyangiitis.
The pathogenesis of lupus -- a highly heterogeneous disease -- is believed to have both genetic and environmental influences, with infection being a prominent environmental factor.
Therefore, to investigate the possibility that S. aureus nasal colonization could have an association with lupus, Alessandri and colleagues enrolled 84 patients from their clinic along with 154 healthy blood donors as controls.
Most of the lupus patients were women. Mean age was 41 and mean disease duration was almost 12 years. Involvement of the joints was present in 68%, of the skin in 69%, and of the kidney in 37%.
All had antinuclear antibodies present, 82% had anti-ds-DNA, 29% had anti-SSA antibodies, 12% had anti-SSB, and 16% had anti-Sm antibodies. Twenty of the patients also had other autoimmune diseases such as antiphospholipid syndrome or Sjogren's syndrome in addition to their lupus.
A total of 21.4% of patients with lupus were found to be carriers of S. aureus, which was similar to the rate of 28.6% among healthy controls, and all cases were methicillin-sensitive.
Along with high rates of renal involvement, carriers more often had lupus skin manifestations compared with noncarriers (22.1% vs 15.1%), although this was not a significant difference.
And in addition to high rates of anti-ds-DNA antibodies, S. aureus carriers also had greater prevalence of these autoantibodies compared with noncarriers:
- Anti-Sm: 22.2% vs 9.1% (P=0.01)
- Anti-SSA: 44.4% vs 21.1%, (P=0.0008)
- Anti-SSB: 16.6% vs 6.1%, (P=0.03)
- Anti-RNP: 16.6% vs 6.1%, (P=0.03)
"Carriers had a significantly higher prevalence of anti-SSA and anti-SSB antibodies, which are associated with cutaneous involvement. In addition, anti-ds-DNA and anti-Sm antibodies, which are associated with renal involvement, were present in S. aureus-positive patients," the authors noted.
In contrast, complement levels were lower among noncarriers. Low C3 levels were seen in 29.7% of noncarriers compared with 16.6% of carriers (P=0.01), while C4 levels were low in 32.8% of noncarriers compared with 22.2% of carriers (P=0.03).
Persistently high disease activity was noted in the year before enrollment among carriers, although this was not statistically significant (27.7% vs 17.2%).
Significantly more carriers were receiving steroid treatment (83.3% vs 65.1%, P=0.01), but there was no difference in weekly prednisone dose (40.2 mg vs 49.1 mg).
"It should be considered that glucocorticoid treatment could determine skin abnormalities. In particular, permeability barrier homeostasis and stratum corneum integrity and cohesion could be modified by glucocorticoid treatment," the researchers explained.
They also offered potential explanations for why carriage of S. aureus might contribute to lupus pathogenesis, stating that its presence "seems to induce an inflammatory response by exposing staphylococcal superantigen, molecular mimicry, causing increased toll-like receptor signaling in leukocytes, and inducing neutrophil extracellular traps."
Carriage also could lead to T-cell activation, they suggested. "Data from the literature demonstrated that staphylococcal enterotoxins could bind directly the major histocompatibility complex class II of antigen-presenting cells. The presentation to T cells leads to massive nonspecific activation of the immune system, by stimulating around 20% of the naive T-cell population."
A limitation of the study was the use of morphological evaluation for S. aureus identification. In addition, it cannot be determined whether the association of carriage with the distinct disease phenotype "is an epiphenomenon rather than a causal factor."
Nonetheless, further investigation into the skin microbiome in lupus is warranted, they concluded.
Alessandri and co-authors disclosed no relevant relationships with industry.
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